Regulation of the production of soluble IL-4 receptors in murine cutaneous leishmaniasis. The roles of IL-12 and IL-4.
These studies were undertaken with the purpose of elucidating the key signals involved in the regulation of the production of soluble interleukin-4 receptors (sIL-4R) in mice during Th1 and Th2 responses to infection with the parasite Leishmania major. Our results showed that the production of sIL-4R was consistently higher in lymph node cell cultures from animals mounting a predominant Th2 response (BALB/c mice), and that sIL-4R production paralleled that of IL-4 in both mouse strains, even in the presence of a dominant Th1 response (C3H/FeJ mice). Consistently, administration of anti-IL-12 antibodies to infected C3H/ FeJ mice induced a switch from a Th1- to a Th2-type response and resulted in enhanced production of sIL-4R. Addition of rIL-12 to splenic cell cultures, however, was found not to have a direct effect on sIL-4R production induced by IL-4 or T cell mitogens. Moreover, the production of sIL-4R appears to be little influenced by Th1-produced cytokines, inasmuch as recombinant interferon-gamma or supernatants derived from antigen-stimulated Th1 clones did not affect the production of sIL-4R by activated splenic cultures. Despite its correlation with Th2 responses, the presence of IL-4 was not an absolute requirement for the up-regulation of the expression of sIL-4R because increased levels could be induced on cells obtained from IL-4-/- mice. These results indicate that, although enhanced sIL-4R production is a feature related to the activation and/or generation of Th2 responses, it is not absolutely dependent on IL-4 or directly inhibited by IL-12 or Th1 cytokines.
Fernandez-Botran
R
R
Department of Pathology and Laboratory Medicine, University of Louisville, Kentucky 40292, USA. rafael@louisville.edu
Chilton
P M
PM
Hondowicz
B D
BD
Vetvickova
J
J
Yan
J
J
Jones
W
W
Scott
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019948:Receptors, Interleukin-4 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma