Role of IL-6 in directing the initial immune response to schistosome eggs.
The eggs of Schistosoma mansoni are strong inducers of a Th2 response, and previous work has shown that Ag-specific IL-6 is produced within 24 h after the injection of eggs into mice. Investigations to determine the role of IL-6 in orchestrating the early response to schistosome eggs have revealed that IL-12 is rapidly produced in lymph node cell cultures from egg-injected mice. This "early" IL-12 primes for the production of IL-6 and IFN-gamma, for in IL-12-/- mice egg injection fails to stimulate increased production of either of these cytokines. Furthermore, IL-6 also up-regulates IL-10 production which, together with IL-6, negatively regulates IL-12 and IFN-gamma production. Finally, IL-10 down-regulates the production of its inducer, IL-6. These data indicate that the anti-inflammatory role of IL-6 may be effected through negative regulation of type 1 (IFN-gamma) and type 1-associated (IL-12) cytokines either directly (by IL-6) or indirectly (through the induction of IL-10) and suggest that one mechanism by which eggs may support the development of Th2 responses is through the negative regulation of the type 1 response.
La Flamme
A C
AC
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
MacDonald
A S
AS
Pearce
E J
EJ
D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D004357:Drug Synergism; D005260:Female; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010063:Ovum / Q000276:immunology*; D012550:Schistosoma mansoni / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000947:Antigens, Helminth; D015850:Interleukin-6; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma