Altered production of IFN-gamma? And other inflammation-related cytokines by mycobacteria- stimulated peripheral blood mononuclear cells from rheumatoid arthritis patients.
Peripheral blood mononuclear cells taken from 32 patients with Rheumatoid Arthritis (RA) receiving neither steroids nor methotrexate and 34 healthy controls were examined for lymphoproliferation in the presence of ultrasonic extracts of 14 different mycobacterial species or serotypes, of an extract of Candida albicans and of 2 mitogens. Additionally, cells were incubated for 96 hours alone, or with Mycobacterium tuberculosis (M.tb) sonicate or Concanavalin-A (Con-A), and supernatants were tested for a range of cytokines. Lymphocytes of rheumatoid patients were less reactive than controls to all the mycobacterial preparations, but no different in their responses to mitogens. Stimulation of patients' cells with M.tb sonicate induced significantly less interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) but more transforming growth factor- beta (TGF-beta) than controls. Even stimulation with Con-A induced much less IFN-gamma in patient's cells than in those of controls. The combination of reduced responses to the mycobacterial reagents and reduced stimulation of type 1 cytokines by the sonicate of M.tb, suggests reduced responsiveness to group i, common mycobacterial antigens. Such findings need not indicate involvement of mycobacteria specifically in the disease aetiology, but provide novel information on the immunopathological abnormalities, which may explain the reported increased susceptibility to mycobacteria of RA patients.
Rondelli
F M
FM
Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, Rosario (2000), Argentina.
Mahuad
C V
CV
Gentiletti
A
A
Goñi
M
M
Pons-Estel
B
B
Bottasso
O
O
Stanford
J L
JL
Bay
M L
ML
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D000939:Epitopes; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007244:Infectious Mononucleosis / Q000276:immunology; D007249:Inflammation / Q000097:blood*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007962:Leukocytes / Q000382:microbiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000276:immunology; D009159:Mycobacteriaceae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D000939:Epitopes; D008934:Mitogens; D007371:Interferon-gamma