Immunological studies in uremic and kidney transplanted patients.
Some aspects of the cellular in vitro immune response were studied in uremic and kidney transplanted patients. In particular, the immunosuppressive effects of glucocorticoids were examined in uremic patients and in cadaver kidney graft recipients with special reference to clinical kidney transplantation. 1) In vitro, lymphocytes from patients on hemodialysis had impaired responses to stimulation with mitogen. Variations in the culture conditions including changes in; (i) mitogen concentrations, (ii) culture periods, (iii) aerobic growth conditions, (iiii) and cellular synthesis of prostaglandins did not normalize the uremic lymphocyte response. 2) A possible effect of hemodialysis per se could not be excluded. However, in short term experiments accumulation in uremic plasma of inhibitory factors and/or deprivation of supportive factors could only partly explain the decreased cell responses. 3) In vitro, glucocorticoids inhibit the proliferation of mitogen stimulated normal lymphocytes in a dose-dependent way. Moreover, the in vitro immunosuppressive effects of some glucocorticoids did not correlate with their anti-inflammatory potencies. In uremic cell cultures the in vitro lymphocyte sensitivity to glucocorticoids was 5-8 fold increased in comparison to the control cultures. 4) Lymphocytes from patients on peritoneal dialysis (CAPD) and non-dialyzed uremic patients had normal transformation responses but were also very sensitive in vitro to glucocorticoids. 5) Cytotoxic effector cell functions (NK and K) remained normal in hemodialyzed patients which is in contrast to the decreased transformation responses presupposing interleukin-2 (IL-2) dependent cell proliferation (DNA synthesis). Furthermore, both control and uremic NK and K cell functions were resistant in vitro to the suppressive effects of glucocorticoids. 6) The decreased mitogen response of patients on hemodialysis was improved by addition of IL-2 to the cell cultures. Moreover, IL-2 normalized the increased uremic sensitivity in vitro to glucocortiooids. In accordance, the production of IL-2 was decreased in mitogen stimulated cell cultures from patients on hemodialysis. There was no evidence that the impaired transformation responses of lymphocytes from patients on hemodialysis was due to a lack of cells positive for IL-2 receptors. These results suggested that a deficient production of IL-2 may be part of; (i) the decreased transformation response (ii) and the increased sensitivity in vitro to glucocorticoids of lymphocytes from hemodialyzed patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Langhoff
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Medical Department P, Rigshospitalet, Copenhagen.
D003602:Cytotoxicity, Immunologic; D005938:Glucocorticoids / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D016030:Kidney Transplantation; D008213:Lymphocyte Activation / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology; D014511:Uremia / Q000276:immunology*
D005938:Glucocorticoids; D007376:Interleukin-2; D015375:Receptors, Interleukin-2