Regulation of the production of soluble IL-4 receptors in murine cutaneous leishmaniasis. The roles of IL-12 and IL-4.

Abstract

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.

• Authors: R Fernandez-Botran, P M Chilton, B D Hondowicz, J Vetvickova, J Yan, W Jones 3rd, P Scott
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 66 Issue 3 Pg. 481-8 (Sep 1999) ISSN: 0741-5400 [Print] United States
• PMID: 10496319 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Culture Media, Conditioned
• Receptors, Interleukin-4
• Recombinant Proteins
• Interleukin-12
• Interleukin-4
• Interferon-gamma

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Cells, Cultured
• Culture Media, Conditioned (chemistry, pharmacology)
• Interferon-gamma (pharmacology)
• Interleukin-12 (immunology, pharmacology, physiology)
• Interleukin-4 (deficiency, genetics, physiology)
• Leishmania major (immunology)
• Leishmaniasis, Cutaneous (genetics, immunology, metabolism)
• Lymph Nodes (metabolism)
• Lymphocyte Activation (drug effects)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Interleukin-4 (metabolism)
• Recombinant Proteins (pharmacology)
• Solubility
• Specific Pathogen-Free Organisms
• Spleen (immunology)
• Th1 Cells (immunology, metabolism)
• Th2 Cells (immunology, metabolism)