Expression of IFN gamma, coexpression of TNF alpha and matrix metalloproteinases and apoptosis of T lymphocytes and macrophages in granuloma annulare

Granuloma annulare, a prototype noninfectious granulomatous dermatitis, is morphologically characterized by a necrobiotic core surrounded by a cellula r infiltrate, Because of many morphological similarities to tuberculosis, g ranuloma annulare has been suggested to represent a delayed-type hypersensi tivity (Th1) reaction in the course of which inflammatory cells elicit matr ix degradation, In the present study we (1) investigated the expression of interferon-gamma as the most important Th1-associated cytokine, (2) sought in situ evidence for the coexpression of the proinflammatory cytokine tumor necrosis factor-a and cytokine-regulated matrix metalloproteinases 2 (gela tinase A) and 9 (gelatinase B), and (3) sought to determine whether shrunke n cells seen within necrobiotic areas of granuloma annulare are apoptotic c ells, In situ hybridization combined with immunofluorescence showed that la rge numbers of infiltrating CD3(+) lymphocytes express interferon-gamma, Ap plication of catalyzed signal amplification in immunodetection revealed tha t the vast majority of CD3(+) lymphocytes and CD68(+) macrophages contained tumor necrosis factor-alpha. Immunohistochemistry demonstrated that macrop hages producing tumor necrosis factor-ct coexpress matrix metalloproteinase s 2 and 9, In situ end-labeling combined with immunofluorescence detected f ew apoptotic T cells in perivascular regions and numerous apoptotic macroph ages within necrobiotic areas, These results suggest that in granuloma annu lare interferon-gamma(+) Th-1 lymphocytes may cause a delayed-type hypersen sitivity reaction whereby macrophages are differentiated to aggressive effe ctor cells expressing tumor necrosis factor-alpha and matrix metalloprotein ases, In parallel, activation-induced apoptosis in lymphocytes and macropha ges may serve to restrict the destructive potential of the inflammatory cel ls.