Cell-mediated immunity in sarcoidosis: effect of corticosteroids.
The paradoxical skin response in sarcoidosis is a delayed hypersensitivity skin response to an antigen such as PPD which can be elicited only when corticosteroid is present and not when it is absent. Approximately half the tuberculin-negative patients with sarcoidosis are paradoxical responders. In vitro culture of lymphocytes of 10 paradoxical responders with sarcoidosis demonstrated that a response to purified protein derivative of tuberculin (PPD) could be elicited in every patient on at least one occasion both by thymidine uptake and by macrophage migration inhibition factor (MIF) production. The response, when present, was generally at a lower level that that of normal control lymphocytes. No factor was found in the serum which could explain the low activity of the sarcoid lymphocytes in cross-over experiments with normal cells and serum. Hydrocortisone added to the in vitro lymphocyte cultures abolished lymphocyte transformation with respect to both thymidine uptake and MIF production. Varying the conditions of lymphocyte exposure to hydrocortisone, dose, duration of culture and conditions of exposure to hydrocortisone (before and after antigen) failed to enhance lymphocyte stimulation at each and every attempt. Cultures of lymphocytes obtained after oral administration of prednisone were inhibited just as if hydrocortisone had been added in vitro. However, at this time the skin responses of six out of seven patients showed delayed hypersensitivity to previously injected PPD. It is suggested that in addition to the lymphocyte defect paradoxical responders have a defect in their ability to express delayed hypersensitivity. The effect of corticosteroids is to aggravate the lymphocyte defect but in many patients the skin defect is overcome or corrected.
D004305:Dose-Response Relationship, Drug; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis; D012507:Sarcoidosis / Q000276:immunology*; D012882:Skin Tests
D008263:Macrophage Migration-Inhibitory Factors; D006854:Hydrocortisone