Kinetics of cytokine production in experimental systemic lupus erythematosus: involvement of T helper cell 1/T helper cell 2-type cytokines in disease.
We followed cytokine production from induction through disease progression in a murine model of experimental systemic lupus erythematosus (SLE). SLE was induced by immunization with the human monoclonal anti-DNA Ab that bears the common Id designated 16/6 Id. BALB/c and C3H.SW mice that are susceptible to SLE induction and C57BL/6 mice that are resistant were immunized with the 16/6 Id. Cytokine production was tested periodically for 7 mo. Increased production of IL-2 and IFN-gamma, the Th1-type cytokines, was detected in BALB/c and C3H.SW mice 2 to 4 mo following immunization. IL-4 and IL-10, the Th2-type cytokines predominated later in disease course, and peaked 5 mo following disease induction. At this stage the Th1 type cytokines dropped to levels below those observed in controls. IL-4 production also dropped rapidly to very low levels, while IL-10 production decreased but remained above control levels. The ratio of IgG2a/IgG1 of DNA and 16/6 Id-specific Abs peaked at 2 mo following disease induction and decreased later, in concordance with the higher production of Th2-type cytokines. Thus, the development of experimental SLE in mice involves two stages: increased production of Th1-type, followed by increased induction of Th2-type cytokines. High levels of the proinflammatory cytokines, TNF-alpha and IL-1, were maintained throughout disease course. No significant changes were detected in the cytokine profile of C57BL/6 immunocytes following immunization with the 16/6 Id, supporting the possible role of the cytokine network in SLE.
Segal
R
R
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Bermas
B L
BL
Dayan
M
M
Kalush
F
F
Shearer
G M
GM
Mozes
E
E
D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D005260:Female; D007114:Immunization; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines