Blockade of IFN-gamma does not affect the arthritogenicity of T cells generated during the induction of adjuvant arthritis but exacerbates the polyarthritis produced by adoptive transfer of arthritogenic effector cells.

IFN-gamma production is prominent in some models of autoimmune disease, including adjuvant arthritis (AA), but the role of IFN-gamma in the pathogenesis of these diseases is uncertain. Experimental manipulation (administration of cytokine, blocking cytokine action with specific antibody, disruption of genes encoding the cytokine or its receptor) has revealed both pro- and anti-inflammatory effects, depending on the nature of the manipulation and the timing of the treatment. We examined separately the effects of cytokine blockade during the afferent and efferent phases of AA in Dark Agouti rats, using an adoptive transfer system. Effects of IFN-gamma on the efferent phase were investigated by treating recipients with mAb DB-1, which blocks the activity of rat IFN-gamma. When treatment was commenced before cell transfer, the resulting polyarthritis was more severe than in controls treated with normal IgG. Commencing treatment after the adoptively transferred disease had become established caused neither amelioration nor exacerbation, but did cause some delay in resolution. In contrast, treatment of donors did not appear to affect the generation of arthritogenic cells. The main effect of IFN-gamma appears to be modulation of the arthritogenicity of the migratory effector T cells that can transfer AA.

Leukocyte networks and human endometrial remodelling.

Remodelling of the human endometrium occurs during the normal menstrual cycle. This process involves the disintegration of the superficial or functionalis layer of the endometrium following the fall in progesterone resulting from the demise of the corpus luteum and the reconstruction of a new layer without scarring. The degradative properties of matrix metalloproteinases (MMP) and their presence in the endometrium during remodelling events suggests that they are effector molecules in this process. The features of menstruation parallel those of an inflammatory response and the abundance of leukocytes in the endometrium prior to the onset of menstruation indicates a role for these cells in the remodelling process. This review examines the relationship between leukocytes and the local production and activation of MMP within the endometrium.