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PMID: 9109438 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Roles of interferon-gamma and interleukin-4 in murine lupus.

The Journal of clinical investigation ·Vol. 99 ·No. 8 ·1997-04-15 ·Pages 1936-46

Peng SL, Moslehi J, Craft J

Abstract

The systemic autoimmune syndrome of MRL/Mp-lpr/lpr (MRL/lpr) mice consists of severe pan-isotype hypergammaglobulinemia, autoantibody production, lymphadenopathy, and immune complex-associated end-organ disease. Its pathogenesis has been largely attributed to helper alphabeta T cells that may require critical cytokines to propagate pathogenic autoantibody production. To investigate the roles of prototypical Th1 and Th2 cytokines in the pathogenesis of murine lupus, IFN-gamma -/- and IL-4 -/- lupus-prone mice were generated by backcrossing cytokine knockout animals against MRL/lpr breeders. IFN-gamma -/- animals produced significantly reduced titers of IgG2a and IgG2b serum immunoglobulins as well as autoantibodies, but maintained comparable levels of IgG1 and IgE in comparison to cytokine-intact controls; in contrast, IL-4 -/- animals produced significantly less IgG1 and IgE serum immunoglobulins, but maintained comparable levels of IgG2a and IgG2b as well as autoantibodies in comparison to controls. Both IFN-gamma -/- and IL-4 -/- mice, however, developed significantly reduced lymphadenopathy and end-organ disease. These results suggest that IFN-gamma and IL-4 play opposing but dispensable roles in the development of lupus-associated hypergammaglobulinemia and autoantibody production; however, they both play prominent roles in the pathogenesis of murine lupus-associated tissue injury, as well as in lpr-induced lymphadenopathy.

MeSH Terms
Animals Autoantibodies/blood Female Immunoglobulin Isotypes/blood Interferon-gamma/deficiency,genetics,physiology Interleukin-4/deficiency,genetics,physiology Kidney/pathology Liver/pathology Lupus Erythematosus, Systemic/etiology,genetics,immunology Male Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Inbred MRL lpr Mice, Knockout Mutation Salivary Glands/pathology
Chemicals
Autoantibodies Immunoglobulin Isotypes Interleukin-4 Interferon-gamma
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Peng S L
Section of Rheumatology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Moslehi J
Craft J
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119361
Published
1997-04-15
Pages
1936-46
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508018
Subset
IM
Grants
NIAMS NIH HHS · AR40072 · United States
NIAMS NIH HHS · AR44076 · United States
External Links
PubMed source DOI: 10.1172/JCI119361 PMC Full Text View journal details
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