The influence of prednisolone on the recirculation of peripheral blood lymphocytes in vivo

In humans and in laboratory animals, administration of a single dose of glucocorticosteroids induces a rapid and transient decrease in the numbers of peripheral blood lymphocytes through a redistribution of circulating lymphocytes. This lymphocytopenic effect is an important factor in the immunosuppressive capacity of corticosteroids. We have investigated whether the redistribution is due to an increased influx of circulating lymphocytes from the blood into the lymphoid organs or to a decreased efflux from the organs. Fluoresceinated lymphocytes were injected intravenously in unrestrained normal and prednisolone-treated rabbits and the distribution curves in the peripheral blood were analysed on the basis of a two-compartment model (known from pharmacokinetic studies). In this way, it is shown that the rapid fall in peripheral blood lymphocytes numbers induced by prednisolone is due to a decreased efflux of circulating lymphocytes from the lymphoid organs. In addition, it is demonstrated that prolonged infusion of prednisolone leads to an altered distribution pattern of the circulating lymphocytes among the organs

Cyclosporine A does not prevent expression of biologically active IL 2 receptors in vitro

In this study, we show that CsA does not affect the expression of IL 2 receptors. Moreover, these IL 2 receptors are capable of transducing signals, as measured by a rise in intracellular pH

Whole-blood lymphocyte cultures

A simple and reproducible method is desribed for the measurement of proliferative responses of peripheral blood lymphocytes in whole blood upon stimulation with horse anti-human lymphocyte serum (ALS), phytohaemagglutinin (PHA) or a monoclonal antibody (mAb) directed against CD3. Only small aliquots of blood are needed and separation procedures are not necessary. Since the method proved to be very reproducible and showed little variation, reference values of proliferation, expressed in cpm per 15 μ1 blood and cpm per 103 CD3+ lymphocytes, were determined based upon the 5th and the 2.5th percentile of the distribution of the values in our reference population. In addition, the use of whole blood lymphocyte cultures in longitudinal studies of immunocompromised individuals is demonstrated

Interleukin-6 and neopterin in renal transplant recipients: a longitudinal study

Serum and urine interleukin-6 (IL-6) levels and serum neopterin/creatinine ratios were longitudinally studied in 86 renal transplant recipients until 4 months after transplantation. During acute rejection and acute tubular necrosis (ATN), serum and urine IL-6 levels were elevated compared to during stable transplant function (P<0.001). During acute rejection, serum IL-6 levels increased at least 2 days before plasma creatinine started to rise (P<0.05), indicating its early involvement in the rejection process. During cytomegalovirus (CMV) disease, serum, but not urine, IL-6 levels were higher (P<0.01), and serum neopterin/creatinine values were higher than during stable transplant function, ATN, or acute rejection (P<0.01). No significant differences with stable transplant function occurred during cyclosporin A toxicity. Measurement of serum IL-6 provided a sensitivity of 84% and a specificity of 85% for the diagnosis of acute rejection episodes not coinciding with ATN. All cases of CMV disease could be diagnosed by measurement of serum neopterin/creatinine, which provided a specificity of 73%

The influence of immunosuppressive treatment on immune responsiveness in vivo in kidney transplant recipients

In this study, we have compared the influence of CsA and pred/aza on the immunocompetence in man. Therefore, kidney-transplant recipients were tested for their primary keyhole limpet hemocyanin and secondary (tetanus and KLH) humoral immune responses and their primary dinitrochlorobenzene and secondary (recall antigens) cellular immune responses. We demonstrate that primary immune responses are inhibited by CsA, whereas secondary immune responses are relatively résistant. Pred/aza therapy seems to inhibit all cellular immune responses, as we demonstrated before, as well as the primary humoral immune responses. Secondary humoral immune responses are only slightly affected by pred/aza. Our results provide a strong argument for starting immunosuppression with CsA, either with or without a low-dose pred

Cellular and humoral immunity in various cohorts of male homosexuals in relation to infection with human immunodeficiency virus

The relationship between infection with human immunodeficiency virus (HIV) and various immunological parameters was studied in: (a) healthy controls; (b) homosexual individuals from the AIDS risk group without anti-HIV antibodies; (c) idem, but with anti-HIV antibodies; (d) patients with persistent generalized lymphadenopathy (PGL); (e) patients with AIDS-related syndrome; (f) patients with AIDS and opportunistic infections. In each group; consisting of 15-20 individuals, the following parameters were studied: absolute numbers of CD4+ and CD8+ cells; ratio CD4+ CD8+; cellular immune responses as measured in vivo by delayed-type hypersensitivity (DTH) and in vitro; and antibody response in vivo after immunization with a low dose of keyhole limpet haemocyanin. Healthy HIV antibody-positive individuals and patients with persistent generalized lymphadenopathy already showed a decreased CD4+ CD8+ ratio, mainly due to an increase in the number of CD8+ cells. The ratio in the AIDS-related syndrome and AIDS groups was even lower, but this was now due to low numbers of CD4+ cells while the number of CD8+ cells was normal. The lymphocyte proliferative response was low in the HIV antibody-positive group, normal in the group with persistent generalized lymphadenopathy and profoundly decreased in the AIDS-related syndrome and AIDS groups. DTH was enhanced in the PGL group and diminished in both ARC and AIDS. Compared to healthy controls, the antibody response upon immunization with a low dose of keyhole limpet haemocyanin was depressed (although not absent) in all groups sstudied, even in HIV anttibody-negative hmosexuals. In the HIV antibody-positive group, the severity of the impairment of the various parameters of immunocompetence was not related to the presence of HIV antigenaemia