CD4+ T cell inducible immunoregulatory cytokine response in rheumatoid arthritis.
OBJECTIVE
Monocytes and CD4+/CD8+ T cells produce immunoregulatory cytokines that participate in the pathogenesis of various immune disorders. We investigated the secretion of Th1-Th2 cell response cytokine production of CD4+/CD8+ T cells from the synovial fluid (SF) and blood of patients with rheumatoid arthritis (RA).


METHODS
Blood and SF purified monocytes, CD4+ and CD8+ T cells were stimulated with bacterial lipopolysaccharides or anti-CD3 antibody, and secretion of various cytokines was determined by bioassay or ELISA:


RESULTS
Monocytes from SF and blood of patients with RA produced highly elevated levels of interleukin-1 alpha (IL-1 alpha), IL-6, tumor necrosis factor-alpha (TNF-alpha), and granulocyte macrophage colony stimulating factor (GMCSF), the leading mediators of inflammation. However, CD4+ T cells secreted deficient levels of IL-2 and interferon-gamma (IFN-gamma), but higher levels of IL-4 and IL-10, the typical immunoregulatory Th2 cell response cytokines. CD8+ T cells also produce elevated levels of IL-4 and IL-10 but almost normal levels of IFN-gamma in this disease.


CONCLUSIONS
The cytokine produced by monocytes (IL-alpha, IL-6, TNF-alpha, and GMCSF) and by CD4+ T cells Th2 cell responses (IL-4 and IL-10) may exert immunopathologic and immunoregulatory effects in SF and thus mediate some of the clinical manifestations of RA.
al-Janadi
N
N
Department of Medicine, College of Medicine, King Saud University, Abha, Saudi Arabia.
al-Dalaan
A
A
al-Balla
S
S
Raziuddin
S
S
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology; D007378:Interleukins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D018836:Inflammation Mediators; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor