Quantitative polymerase chain reaction analysis reveals marked overexpression of interleukin-1 beta, interleukin-1 and interferon-gamma mRNA in the lymph nodes of lupus-prone mice.
The nature of the stimuli driving autoantibody production in systemic lupus erythematosus (SLE) is unclear, but cytokines are believed to play an important role. Since cytokines primarily appear to act locally at the tissue level, we analysed mRNA expression of several cytokines (IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, IFN gamma, TNF alpha, TNF beta and TGF beta 1) in the lymph nodes of lupus-prone mice, in models of early onset disease. We constructed a multispecific competitor fragment that allowed quantification of these cytokine transcripts by competitive PCR assay. The results reveal considerable overexpression of IL-1 beta, IL-10 and IFN gamma transcripts in SLE-prone MRL-lpr/lpr (MRL/l) and BXSB male (BXSBm) mice, but with some strain differences. IFN gamma was most markedly augmented in MRL/l mice (in some cases over 100-fold greater than control mice), IL-1 beta was most severely overexpressed in BXSBm mice while IL-10 was equally increased in both strains. In addition, TGF beta 1 expression was moderately elevated in the lymph nodes of BXSBm (but not MRL/l) mice. We found no abnormality in the expression of the other cytokines. Cytokine transcript levels were only slightly altered at 4 weeks of age, but were elevated from 10 to 22 weeks of age. The latter phase corresponds to a period where lupus-like disease escalates, resulting in frequent mortality. Interestingly, our results do not reveal a clear Th1 or Th2 cytokine expression pattern in these lupus-prone mice. IL-1 beta, IFN gamma and IL-10 are pleiotropic cytokines with pro-inflammatory and B-cell stimulatory effects. These results point to certain cytokines as potential targets for immunotherapy in lupus.
Prud'homme
G J
GJ
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Kono
D H
DH
Theofilopoulos
A N
AN
D000367:Age Factors; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics*; D007375:Interleukin-1 / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods / Q000706:statistics & numerical data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D017931:DNA Primers; D007375:Interleukin-1; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma