Role of interleukin-15 and interleukin-18 in the secretion of sil-6r and sgp130 by human neutrophils

Relevanta dokument
FORSKNINGSKOMMUNIKATION OCH PUBLICERINGS- MÖNSTER INOM UTBILDNINGSVETENSKAP

Questionnaire on Nurses Feeling for Hospital Odors

Stiftelsen Allmänna Barnhuset KARLSTADS UNIVERSITET

SWESIAQ Swedish Chapter of International Society of Indoor Air Quality and Climate

Measuring child participation in immunization registries: two national surveys, 2001

Isolda Purchase - EDI

Health café. Self help groups. Learning café. Focus on support to people with chronic diseases and their families

Pre exam I PATHOLOGY FOR MEDICAL STUDENTS

Preschool Kindergarten

Viktig information för transmittrar med option /A1 Gold-Plated Diaphragm

Introduktion till vetenskaplig metodik. Johan Åberg

KOL med primärvårdsperspektiv ERS Björn Ställberg Gagnef vårdcentral

Writing with context. Att skriva med sammanhang

SUPPLEMENTARY FIGURE LEGENDS

Kristina Säfsten. Kristina Säfsten JTH

Validering av kvalitetsregisterdata vad duger data till?

Inflammation och immunologi - vad en psykiater bör veta Susanne Bejerot, Daniel Eklund, Eva Hesselmark, Mats Humble

Labokha AA et al. xlnup214 FG-like-1 xlnup214 FG-like-2 xlnup214 FG FGFG FGFG FGFG FGFG xtnup153 FG FGFG xtnup153 FG xlnup62 FG xlnup54 FG FGFG

Aktivering av signalen via TCR involverar många steg som måste stämma:

Cancersmärta ett folkhälsoproblem?

Information technology Open Document Format for Office Applications (OpenDocument) v1.0 (ISO/IEC 26300:2006, IDT) SWEDISH STANDARDS INSTITUTE

CHANGE WITH THE BRAIN IN MIND. Frukostseminarium 11 oktober 2018

District Application for Partnership

Room E3607 Protein bioinformatics Protein Bioinformatics. Computer lab Tuesday, May 17, 2005 Sean Prigge Jonathan Pevsner Ingo Ruczinski

The Finite Element Method, FHL064

Tentamen 12/ Medicinsk Teknik Fördjupningskurs Implantat och biomaterial, 7E1112 (KTH), MTF003 (KI)

SUPPLEMENTARY INFORMATION

Methods to increase work-related activities within the curricula. S Nyberg and Pr U Edlund KTH SoTL 2017

Senaste trenderna från testforskningen: Passar de industrin? Robert Feldt,

SkillGuide. Bruksanvisning. Svenska

FaR-nätverk VC. 9 oktober

Is it possible to protect prosthetic reconstructions in patients with a prefabricated intraoral appliance?

(Aloe vera L.) Downloaded from jcb.sanru.ac.ir at 20: on Thursday October 24th Liliaceae

Materialplanering och styrning på grundnivå. 7,5 högskolepoäng

Grafisk teknik IMCDP IMCDP IMCDP. IMCDP(filter) Sasan Gooran (HT 2006) Assumptions:

Fysisk aktivitet och hjärnan

EVALUATION OF ADVANCED BIOSTATISTICS COURSE, part I

Syns du, finns du? Examensarbete 15 hp kandidatnivå Medie- och kommunikationsvetenskap

Den framtida redovisningstillsynen

Rättningstiden är i normalfall 15 arbetsdagar, annars är det detta datum som gäller:

Module 6: Integrals and applications

UTLYSNING AV UTBYTESPLATSER VT12 inom universitetsövergripande avtal

Förändrade förväntningar

Kursplan. JP1040 Japanska III: Språkfärdighet. 15 högskolepoäng, Grundnivå 1. Japanese III: Language Proficiency

Könsfördelningen inom kataraktkirurgin. Mats Lundström

Skill-mix innovation in the Netherlands. dr. Marieke Kroezen Erasmus University Medical Centre, the Netherlands

Grafisk teknik IMCDP. Sasan Gooran (HT 2006) Assumptions:

Kursbok: The immune system Peter Parham. Kapitel 5 Hela skall läsas och kunnas utom: Kapitel 5.5; Fig. 5.9 Kapitel 5.11 och 5.12

The cornerstone of Swedish disability policy is the principle that everyone is of equal value and has equal rights.

The Algerian Law of Association. Hotel Rivoli Casablanca October 22-23, 2009

Beijer Electronics AB 2000, MA00336A,

Klassificering av brister från internaudit

Att använda immunförsvaret vid behandling av cancer

Consumer attitudes regarding durability and labelling

Assigning Ethical Weights to Clinical Signs Observed During Toxicity Testing

EXPERT SURVEY OF THE NEWS MEDIA

Luftfartsavdelningen Sektionen för flygutbildning MANUALER VÄLKOMNA EN KORT SAMMANFATTNING AV INNEHÅLLET I RESPEKTIVE MANUAL

Swedish adaptation of ISO TC 211 Quality principles. Erik Stenborg

Bilaga 5 till rapport 1 (5)

Alias 1.0 Rollbaserad inloggning

Inkvarteringsstatistik. Göteborg & Co

ASSESSMENT AND REMEDIATION FOR CHILDREN WITH SPECIAL EDUCATIONAL NEEDS:

EXTERNAL ASSESSMENT SAMPLE TASKS SWEDISH BREAKTHROUGH LSPSWEB/0Y09

Grafisk teknik. Sasan Gooran (HT 2006)

The Arctic boundary layer

Teenage Brain Development

Hur fattar samhället beslut när forskarna är oeniga?

REHAB BACKGROUND TO REMEMBER AND CONSIDER

Manhour analys EASA STI #17214

Resultat av den utökade första planeringsövningen inför RRC september 2005


Om oss DET PERFEKTA KOMPLEMENTET THE PERFECT COMPLETION 04 EN BINZ ÄR PRECIS SÅ BRA SOM DU FÖRVÄNTAR DIG A BINZ IS JUST AS GOOD AS YOU THINK 05

TAKE A CLOSER LOOK AT COPAXONE (glatiramer acetate)

Immunteknologi, en introduktion. Hur man använder antikroppar för att mäta eller detektera biologiska händelser.

Conversational Pedagogical Agents and Gender Annika Silvervarg, Agneta Gulz, Magnus Haake Linköping and Lund University

Maria Fransson. Handledare: Daniel Jönsson, Odont. Dr

KPMG Stockholm, 2 juni 2016

Studenters erfarenheter av våld en studie om sambandet mellan erfarenheter av våld under uppväxten och i den vuxna relationen

Dokumentnamn Order and safety regulations for Hässleholms Kretsloppscenter. Godkänd/ansvarig Gunilla Holmberg. Kretsloppscenter

Sara Skärhem Martin Jansson Dalarna Science Park

Item 6 - Resolution for preferential rights issue.

6 th Grade English October 6-10, 2014

Introduktion till vetenskaplig metodik. Johan Åberg

Signatursida följer/signature page follows

EASA Standardiseringsrapport 2014

8 < x 1 + x 2 x 3 = 1, x 1 +2x 2 + x 4 = 0, x 1 +2x 3 + x 4 = 2. x 1 2x 12 1A är inverterbar, och bestäm i så fall dess invers.

PORTSECURITY IN SÖLVESBORG

1. Compute the following matrix: (2 p) 2. Compute the determinant of the following matrix: (2 p)

Användarhandbok. MHL to HDMI Adapter IM750

D-RAIL AB. All Rights Reserved.

Typografi, text & designperspektiv

Komponenter Removed Serviceable

Cytotoxicitet och blodsjukdomar

Make a speech. How to make the perfect speech. söndag 6 oktober 13

Love og regler i Sverige Richard Harlid Narkos- och Intensivvårdsläkare Aleris FysiologLab Stockholm

Högskolan i Skövde (SK, JS) Svensk version Tentamen i matematik

The Swedish National Patient Overview (NPO)

Styrteknik: Binära tal, talsystem och koder D3:1

SVENSK STANDARD SS :2010

Kursplan. AB1029 Introduktion till Professionell kommunikation - mer än bara samtal. 7,5 högskolepoäng, Grundnivå 1

Transkript:

Short Communication Mediators of Inflammation, 12(3), 179/183 (June 2003) BACKGROUND: Available data indicate that neutrophils (PMN) produce a wide range of cytokines with the potential to modulate immune response. Recent investigation have shown that interleukin (IL)-15 and IL-18 potentiated several functions of normal neutrophils. It has been reported that IL-18-induced cytokine production may be significantly enhanced by coincident addition of IL-15. Aims: In the present study we compared the effect of recombinant human (rh)il-15 and rhil-18 as well as effect of a rhil-15 and rhil-18 combination on the induction secretion of sil-6ra and sgp130 by human neutrophils. Methods: PMN were isolated from heparinized whole blood of healthy persons. The PMN were cultured for 18 h at 378C in a humidified incubator with 5% CO 2. rhil-15 and/or rhil-18 and lipopolysaccharide were tested to PMN stimulation. The culture supernatants of PMN were removed and examined for the presence of sil-6r and sgp130 by human enzyme-linked immunosorbent assay kits. Cytoplasmic protein fractions of PMN were analysed for the presence of sil-6r and sgp130 by western blotting using monoclonal antibodies capable of detecting these proteins. Cells were lysed and cytoplasmic proteins were electrophoresed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The resolved proteins were transferred onto nitrocellulose and incubated with the primary monoclonal antibodies anti-sil-6r and anti-sgp130. The membranes were incubated at room temperature with alkaline phosphatase anti-mouse immunoglobulin G. Immunoreactive protein bans were visualized by an AP Conjugate Substrate Kit. Results and conclusion: The results of our investigation revealed that IL-15 alone, similarly to IL-18, has no significant ability for the regulation of both soluble IL-6 receptors, sil-6r and sgp130, released by human neutrophils. It is interesting to note that the secretion of sgp130 was changed after PMN stimulation with rhil-15 in the presence of rhil-18. The combination of rhil-15 and rhil-18 was shown to induce PMN to secretion relatively higher amounts of sgp130 compared with the stimulation of PMN with rhil-15 alone and rhil-18 alone. The results obtained suggest that IL-15 and IL-18, belonging to the inflammatory cytokines, through the regulation of sgp130 secretion must be also considered as antiinflammatory mediators that may influence the balance reactions mediated by the IL-6 cytokine family. Role of interleukin-15 and interleukin-18 in the secretion of sil-6r and sgp130 by human neutrophils E. Jablonska CA and M. Marcinczyk Department of Immunology, Medical University of Bialystok, Waszyngtona 15A, 15-274 Bialystok, Poland CA Corresponding author Fax: /48 85 424907 E-mail: ewaj@amb.edu.pl Key words: Neutrophils, Soluble interleukin-6 receptor a, Soluble gp130, Interleukin-15, Interleukin-18 Introduction Interleukin (IL)-15 is a pleiotropic cytokine that shares the biological activities with of IL-2. IL-15 uses both b-chains and g-chains of the IL-2 receptor for binding and signalling. The IL-15 receptor (IL- 15R) complex also includes a specific a subunit (IL- 15Ra), distinct from the IL-2Ra chain. IL-15R is expressed on various cells of the immune response, including T cells and B cells, NK cells and, more recently, peripheral blood neutrophils. 1 4 IL-15 plays an important role in both innate and adaptive immunity. It stimulates antigen-driven T-cell proliferation, it has co-stimulatory activity for prolif- ISSN 0962-9351 print/issn 1466-1861 online/03/030179-05 2003 Taylor & Francis Ltd DOI: 10.1080/0962935031000134905 179

E. Jablonska & M. Marcinczyk eration and immunoglobulin (Ig) production by B cells, and is an efficient activator of natural killer and lymphokine activated killer (LAK) cells. 2,4 Recent investigation have shown that IL-15 potentiated several functions of normal neutrophils (PMNs) involved in the innate immune response against invading pathogens. IL-15 was observed to enhance phagocytosis, nuclear factor-kb activation and IL-8 production, and to delay apoptosis of these cells. 4 6 Available data indicate that PMN produce a wide range of cytokines with potential to modulation of immune response. The induction of PMN can lead to the synthesis of cytokines such as IL-1, IL-3, IL-6, IL-8, IL-12, transforming growth factor-b1 interferon-a, granulocyte-colony stimulating factor, granulocyte / macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF)-a, growth-related oncogene (Gro)a, macrophage inflammatory protein (MIP)-1a and MIP-1b. 4,7 It was also found that PMN, similar to the other immune cells, are able to produce naturally occuring proteins that regulate the activity of certain cytokines in biological fluids or in tissue culture supernatants. 7 PMNs have the ability to simultaneous release IL-6 and its regulators: soluble receptors, sil-6ra and sgp130, that control both local and systemic IL-6-mediated responses. 7,8 Because various stimuli are able to induce the cellular release of cytokines and their soluble receptors, it is of interest to examine the role of other inflammatory cytokines in the regulation of IL-6 regulatory protein production. Previous studies in our laboratory have established that IL-18 is a promising candidate for the enhanced secretion of IL-6 by human neutrophils but not for both soluble receptors of IL-6. 8 It is known that IL-18 does not act alone, but in combination with other cytokines, such as IL-12 and/or IL-15. Different combinations of IL-18, IL-12 and IL-15 induce distinct effects. For example, McInnes et al. reported that IL- 18-induced cytokine production may be significantly enhanced by coincident addition of IL-15. 9 In the present study we compared the effect of recombinant human (rh)il-15 and rhil-18 as well as synergistic effect of rhil-15 with rhil-18 on the induction secretion of sil-6ra and sgp130 by human neutrophils. Studies of the interrelations between these mediators may provide new data on the inflammatory network cytokine controlled by these cells. Materials and methods Neutrophils and peripheral blood mononuclear cells (PBMC) were isolated from heparinized (10 U/ml) whole blood of 15 healthy persons by Gradisol G gradient (1.115 g/ml). This method enables simultaneous separation of two highly purified leukocyte 180 Mediators of Inflammation Vol 12 2003 fractions: mononuclear cells containing 95% lymphocytes, and polymorphonuclear cells containing 94% PMN. The purity of isolated PMN and PBMC was determined by May /Grunewald /Giemsa staining. Cells were suspended in the culture medium (RPMI-1640, autologous serum, penicillin and streptomycin) to provide 5/10 6 cells/cm 3. The PMN were cultured in 96-well plates (Falcon) for 18 h at 378C in a humidified incubator with 5% CO 2 (Nuaire TM ). RhIL- 15 (50 ng/ml; R&D Systems, Minneapolis, USA) and/ or rhil-18 (50 ng/ml; R&D Systems) and LPS (50 ng/ ml; Sigma) were tested to stimulate secretion by PMN. After 18 h incubation, the culture supernatants of PMN were removed and examined for the presence of sil-6r and sgp130 by human ELISA kits (R&D Systems) obtained from BIOKOM. Cytoplasmic protein fractions of PMN and PBMC were analysed for the presence of sil-6r and sgp130 by western blotting using monoclonal antibodies capable of detecting these proteins, anti-sil-6r and anti-sgp130, respectively (R&D Systems, from BIO- KOM). Cells were lysed directly by sonication, and cytoplasmic proteins were electrophoresed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The resolved proteins were transferred onto nitrocellulose and incubated with the primary monoclonal antibodies anti-sil-6r and anti-sgp130. The membranes were incubated at room temperature with alkaline phosphatase anti-mouse IgG. Immunoreactive protein bans were visualized by the AP Conjugate Substrate Kit. Results SIL-6Ra and sgp130 protein expression in human PMN and PBMC detected by western blot We used a specific monoclonal antibody directed against the intracellular forms of sil-6r and sgp130 for western blot in PMN and for comparison in PBMC. As shown in Fig. 1, the antibody in human unstimulated and LPS-stimulated PMN and PBMC identified bands of 110 and 55 kda, respectively, from each donor. Western blot analysis showed that the samples of unstimulated PMN and PBMC contained a 110 kda protein that was stained by an anti-sgp130 monoclonal antibody. These samples also contained a 55 kda protein stained by an anti-sil-6r monoclonal antibody. The LPS-stimulated PMN and PBMC expressed a little increased sil-6r protein in comparison with the unstimulated cell lines. In contrast, sgp130 expression in unstimulated and LPS-stimulated cells was on the same level. Comparison of sil- 6R and sgp130 bands indicated that the expression of sgp130 is more intensive than expression of sil-6r.

IL-15 and IL-18 in the secretion of sil-6r and sgp130 FIG. 1. Western blot analysis of sil-6r and sgp130 proteins expression in human PMN and PBMC cells. We showed detection of sil-6r and sgp130 proteins from human unstimulated (line A) and LPS-stimulated (line B), rhil-15-stimulated (line C), rhil- 18-stimulated (line D), and rhil-15/rhil-18-stimulated (line E) PMNs. Whole cell lysates were obtained from fresh PMN of healthy donors. One hundred micrograms of total proteins from PMN were loaded onto a 10% sodium dodecyl sulfate (SDS)- polyacrylamide gel electrophoresis and transferred to a nitrocellulose filter. The filter was incubated with 1:1000 dilution of respective antibody. Sizes of protein standards are given in kilodaltons. One representative western blot of a few independent experiments is shown. SIL-6Ra and sgp130 concentrations in the culture supernatants of PMN detected by enzyme-linked immunosorbent assay In the culture supernatants of unstimulated PMN we observed about 10 times more sgp130 than sil-6ra (23.8 ng/ml and 2.27 ng/ml, respectively). Similar to rhil-18, rhil-15 did not have a significant effect on the release of sil-6ra and sgp130. However, concentrations of both soluble molecules in the culture supernatants of rhil-15-stimulated PMN were non-significantly higher than those in the culture supernatants of rhil-18-stimulated PMN (Fig. 2). LPS stimulation led to a significant increase in the sil-6r secretion by PMN in comparison with unstimulated PMN. We did not observe that kind of relation in the case of sgp130 secretion by PMN (Fig. 2). Release of sil-6r by PMN stimulated with rhil-15 and rhil-18 together were in the levels of sil-6r in the culture of PMN stimulated with rhil-15 only. In contrast to sil-6r, secretion of sgp130 by PMN after stimulation with rhil-15 and rhil-18 together was higher than sgp130 secretion by PMN after stimulation with rhil-15 or rhil-18 alone. Discussion Results of our investigation revealed that IL-15, similarly to IL-18, has no important ability in the regulation of both soluble IL-6 receptors, sil-6r and sgp130, release by human neutrophils. The lack of effect of these cytokines on the sil-6r secretion appears to confirm data demonstrated by other authors who did not find a significant influence of most inflammatory cytokines on sil-6ra production. They demonstrated that IL-1b, IL-6, IL-4, IL-10 or TNF-a did not affect the sil-6r production. 10 We have found that LPS alone stimulated significantly greater amounts of sil-6ra than medium controls, rhil-15 alone, rhil-18 alone as well as the combination of rhil-15 and rhil-18. Similarly, the secretion of sgp130 was independent of the presence of LPS, rhil-15 or rhil-18. It is interesting to note that the secretion of sgp130 was changed after PMN stimulation with rhil-15 in the presence of rhil-18. The combination of rhil-15 and rhil-18 was shown to induce PMN to secretion relatively higher amounts of sgp130 compared with the stimulation of PMN with rhil-15 alone and rhil- 18 alone. Our results indicate that rhil-15 alone and rhil-18 alone, in the used concentrations, do not Mediators of Inflammation Vol 12 2003 181

E. Jablonska & M. Marcinczyk FIG. 2. The concentrations of sil-6r and sgp130 in the culture supernatants of LPS-stimulated, rhil-15-stimulated and rhil-18- stimulated PMN. * Statistical difference with unstimulated cells (pb/0.05). provide signals sufficient to induce soluble IL-6 receptor release by human neutrophils. However, there are available data suggesting a significant role of IL-15 and IL-18 in regulatory function of PMN. 5,6 An important role for IL-18 in the stimulation of PMN activity was recently documented. It has been found that the capacity of PMN to release IL-1b, IL-6, IL-8 and TNF-a was enhanced by the presence of IL-18. 11 13 In our previous study we indicated that IL-18 is also a promising candidate for the enhanced secretion of IL-6 by human neutrophils. However, we have not found a significant effect of IL- 18 on the soluble IL-6 receptors. 12 Additionally, we investigated an effect of IL-15 on the simultaneous secretion of IL-1b and its soluble receptor type II (sil- 1RII) by human neutrophils from normal and tumour-bearing hosts. Our observations indicated that IL-15 induces IL-1b but not sil-1rii release by these cells. 13 182 Mediators of Inflammation Vol 12 2003 The observation indicating various actions of cytokine alone and of cytokine in combination with others are in agreement with reports of different authors. For instance, Fehniger et al. demonstrated that the optimal co-stimulatory monokine combination for GM-CSF production by human natural killer cells was IL-18 and IL-15. 14 A probable explanation for the synergistic effect of IL-18 with IL-15 on the secretion of sgp130 by PMN may be an influence of these cytokines on their specific membrane-bound receptor expression. A recent report characterizing IL-15R and IL-18R expression on PMN revealed that these cells constitutively express both IL-15R and IL-18R mrna and proteins. 5,11 It is possible that IL-15 and IL-18 synergize in inducing sgp130 production by PMN via induction of their membrane-bound receptor expression on PMN, IL-18R can be up-regulated by IL-15 and, conversely, IL-15R may be regulated by the

IL-15 and IL-18 in the secretion of sil-6r and sgp130 presence of IL-18. Further examinations involving estimation of membrane-bound receptor expression are needed to confirm of these suggestions. In conclusion, the results obtained revealed that IL- 15 and IL-18 belonging to the inflammatory cytokines, through the regulation of sgp130 secretion, should also be considered anti-inflammatory mediators that may influence the balance reactions mediated by the IL-6 cytokine family, involving also IL-11, leukemia inhibiting factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF) or cardiotrophin (CT)-1. However, the clinical studies involving inflammation and other pathological conditions may be helpful to explain an importance of these observations. References 1. Mori A, Suko M, Kaminuma O, et al. IL-15 promotes cytokine production of human T helper cells. J Immunol 1996; 156: 2400 /2405. 2. Nishimura H, Yajima T, Naiki Y, et al. Differential roles of interleukin 15 mrna isoforms generated by alternative splicing in immune responses in vivo. J Exp Med 2000; 191: 157/169. 3. Smith XG, Bolton EM, Ruchatz H, Wei X, Liew FY, Bradley JA. Selective blockade of IL-15 by soluble IL-15 receptor a-chain enhances cardiac allograft survival. J Immunol 2000; 165: 3444 /3450. 4. Cassatella MA. The production of cytokines by polymorphonuclear neutrophils. Immunol Today 1995; 16: 21/26. 5. Girard D, Paquet M-E, Paquin R, Beaulieu AD. Differential effects of interleukin-15 (IL-15) and IL-2 on human neutrophils: modulation of phagocytosis, cytoskeleton rearragament, gene expression, and apoptosis by IL-15. Blood 1996; 88: 3176 /3184. 6. McDonald PP, Russo MP, Ferrini S, Cassatella MA. Interleukin 15 (IL-15) induces NF-kB activation and IL-8 production in human neutrophils. Blood 1998; 92: 4828 /4835. 7. Jablonska E, Jablonski J, Holownia A. Role of neutrophils in release of some cytokines and their soluble receptors. Immunol Lett 1999; 70: 191 /197. 8. Jablonska E, Jablonski J. Effect of IL-18 on the release of IL-6 and its soluble receptors: sil-6ra and sgp130 by human neutrophils. Immunol Invest 2002; 31: 159 /167. 9. McInnes IB, Gracie JA, Leung BP, Wei X-Q, Liew FY. Interleukin 18: a pleiotropic participant in chronic inflammation. Immunol Today 2000; 21: 312 /315. 10. Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GA. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J 2001; 15: 43/58. 11. Leung BP, Culshaw S, Gracie JA, et al. A role for IL-18 in neutrophils activation. J Immunol 2001; 167: 2879 /2886. 12. Jablonska E, Izycka A, Jablonski J, Wawrusiewicz N, Piecuch J. Role of IL-18 in the secretion of IL-1b, sil-1rii, and IL-1Ra by human neutrophils. Immunol Invest 2001; 30: 221/229. 13. Jablonska E, Piotrowski L, Kiluk M, Jablonski J, Grabowska Z, Markiewicz W. Effect of IL-15 on the secretion of IL-1b, IL-1Ra and sil-1rii by PMN from cancer patients. Cytokine 2001; 16: 173/177. 14. Fehniger TA, Shah MH, Turner MJ, et al. Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: implications for the innate immune response. J Immunol 1999; 162: 4511/4520. Received 18 February 2003 Accepted 27 March 2003 Mediators of Inflammation Vol 12 2003 183

MEDIATORS of INFLAMMATION The Scientific World Journal Gastroenterology Research and Practice Diabetes Research International Endocrinology Immunology Research Disease Markers Submit your manuscripts at BioMed Research International PPAR Research Obesity Ophthalmology Evidence-Based Complementary and Alternative Medicine Stem Cells International Oncology Parkinson s Disease Computational and Mathematical Methods in Medicine AIDS Behavioural Neurology Research and Treatment Oxidative Medicine and Cellular Longevity