Being expressed in immune cells, cytokine-inducible SH2 protein (CIS) and suppressors of cytokine signaling proteins, SOCS1, SOCS2 and SOCS3, can regulate cytokine signaling and immune responses. To evaluate the possible expressional dysregulation of CIS, SOCS1, SOCS2 and SOCS3 in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients, the transcript levels of these genes in peripheral blood mononuclear cells (PBMCs) from SLE and RA patients were determined and statistically compared with those in PBMCs from normal individuals. It was found that SLE patients with the active disease activity significantly express higher CIS transcript levels than normal individuals and SLE patients with the inactive disease activity, whereas the difference in SOCS1, SOCS2 and SOCS3 transcript levels between normal individuals and SLE patients is not statistically significant. However, transcript levels of these CIS/SOCS genes in RA patients were not significantly different from those in normal individuals, except that treatment with a TNF-alpha-blocking agent in RA patients appears to enhance the CIS transcript expression, but down-regulates the SOCS2 transcript expression in PBMCs. These data suggest that CIS can serve as an SLE disease marker and may be involved in the pathogenesis of SLE, and that TNF-alpha may play an important role in the regulation of CIS and SOCS2 gene expression in PBMCs in vivo.