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Latent inhibition of granulocyte function by cyclosporine A
1Department of Internal Medicine, University of Marburg, Federal Republic of Germany.
Insights
Cyclosporine A (CsA) may partially inhibit granulocyte function, specifically phagocytosis, in kidney transplant patients. This CsA effect correlates with reduced chemiluminescence, suggesting a potential link to increased infection susceptibility.
Area of Science:
- Immunology
- Pharmacology
Background:
- Cyclosporine A (CsA) is known to suppress T and B cell activity.
- Its influence on phagocyte function is less understood, despite reported infections in patients on CsA.
- This study investigates CsA's impact on granulocyte function in kidney transplant recipients.
Purpose of the Study:
- To assess if Cyclosporine A (CsA) alters granulocyte function in patients undergoing immunosuppressive therapy.
- To explore the relationship between CsA blood levels and granulocyte function (chemiluminescence).
Main Methods:
- Chemiluminescence (CL) assay of granulocytes ex vivo after stimulation with PMA or zymosan.
- Analysis of 37 kidney transplant patients and 18 healthy controls.
- Correlation of CL values with CsA, human leukocyte elastase (HLE), and neopterin levels.
Main Results:
- No significant differences in median CL values between therapy groups and controls.
- A significant negative correlation (p=0.05) between CsA blood levels and polymorphonuclear (PMN) maximum CL values.
- CsA inhibited CL for zymosan-stimulated PMN, but not PMA-stimulated PMN, suggesting partial inhibition of phagocytosis.
Conclusions:
- Cyclosporine A (CsA) may exert a partial inhibitory effect on granulocyte phagocytic function.
- This effect appears linked to CsA blood levels and may contribute to increased infection risk.
- CsA also influences macrophages, as indicated by correlations between HLE and neopterin levels.
Abstract:
According to the literature, Cyclosporine A (CsA) is said to suppress specifically the activity of T and B cells. A significant influence on phagocyte function has been neglected. However, aggravated courses of bacterial and fungal infections have been frequently reported under the treatment with CsA, suggesting that a latent depression of phagocytic activity may possibly occur under clinical circumstances. Therefore, this study set out to assess whether CsA can also change granulocyte function under therapy conditions or not. Thirty-seven patients, 3 months-10 years after kidney transplantation being under immunosuppressive treatment with CsA + Prednisolone (n = 25), Azathioprine + Prednisolone (n = 6) and under Prednisolone alone (n = 6) underwent the study. 18 healthy persons served as a normal control group. Granulocyte function was tested ex vivo by chemiluminescence (CL) after stimulation with phorbolmyristate acetate (PMA) and with zymosan (zym) activated autologous or pool-serum. The obtained data were correlated to corresponding serum or plasma levels of CsA, human leukocyte elastase (HLE) and neopterin. Comparing the three therapy groups with the healthy control and with each other no differences could be seen in median CL values; but there was a significant (p = 0.05) negative correlation between CsA blood levels and maximum CL values of PMN. Such inhibition of CL could be calculated for zym but not for PMA stimulated PMN; suggesting that the CsA mediated inhibition of granulocyte function may be only partial and restricted to phagocytosis. In addition, a positive correlation between serum levels of human leukocyte elastase (HLE) and neopterin could be found. This indicates a simultaneous influence of CsA on both PMN and macrophages.