Tuesday, October 10, 2006

Inflammatory mediator sustains SLE T cells

drj writes "Self-reactive antibodies are a hallmark of systemic lupus erythematosus (SLE, lupus), a life-threatening autoimmune disease that disproportionately affects women in their child bearing years. Production of these antibodies is driven by autoreactive T cells that are normally eliminated but persist in SLE patients. Xu and colleagues compared the activities of thousands of genes in the T cells of SLE patients and normal controls. They found that stimulatory conditions that caused normal T cells to be eliminated instead caused SLE T cells to increase their expression of cyclooxygenase-2 (COX-2) and survive. Moreover, inhibiting COX-2 activity reversed the abnormal resistance of SLE T cells. The increased COX-2 was specific to SLE T cells and did not occur in T cells from other autoimmune diseases or cancer cells. Certain COX-2 inhibitors but not others were able to restore normal responses to SLE T cells, providing a rational basis for the use of these drugs for therapy and suggesting approaches to designing more potent and specific therapeutic drugs for use in SLE.
PubMed Xu et al, Nat. Med. February 29, 2004. L, Zhang L, Yi Y, Kang HK, Datta SK. "Human lupus T cells resist inactivation and escape death by upregulating COX-2". Nature Medicine February 29, 2004"

1 comment:

Reuel said...

The Remuzzi group reported increased COX-2 in patients with active lupus nephritis [nih.gov] in 1998 and they demonstrated therapeutic effects of COX-2 inhibitors [nih.gov] in 2001 (in mice).

There are numerous numerous clinical trials [clinicaltrials.gov] studying cyclooxygenase (11) and lupus (26) but none studying Cox-2 in lupus. Have Cox-2 inhibitors been used therapeutically?