IL-9 protects mice from Gram-negative bacterial shock: suppression of TNF-alpha, IL-12, and IFN-gamma, and induction of IL-10.
IL-9 is a T cell-derived cytokine that, similar to the Th2 cytokines IL-4 and IL-10, has been implicated in the response to parasitic infections, allergy, and inflammatory processes. Because both IL-4 and IL-10 can confer protection to mice from septic shock, we investigated whether IL-9 may also be capable of conferring resistance on recipients of an otherwise lethal challenge with Pseudomonas aeruginosa. Prophylactic injections of rIL-9 appeared to be most effective in preventing the onset of a lethal shock, according to a pattern that was both dose dependent and time dependent. The protective effect of IL-9 was correlated with marked decreases in the production of the inflammatory mediators TNF-alpha, IL-12, and IFN-gamma, as well as the induction of the anti-inflammatory cytokine IL-10. Sustained levels of IL-9-specific transcripts could be detected in the spleens of mice recovering from sublethal P. aeruginosa infection. Therefore, IL-9 may be protective in septic shock via a rather unique mechanism involving a complex modulation of inflammatory and anti-inflammatory mediators.
Grohmann
U
U
Department of Experimental Medicine, University of Perugia, Perugia, Italy. grohmann@tin.it
Van Snick
J
J
Campanile
F
F
Silla
S
S
Giampietri
A
A
Vacca
Carmine
C
Renauld
J C
JC
Fioretti
M C
MC
Puccetti
P
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016906:Interleukin-9 / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010431:Pentoxifylline / Q000008:administration & dosage; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D012772:Shock, Septic / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D016906:Interleukin-9; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D010431:Pentoxifylline