Leukocyte Migration Inhibition in Propranolol-induced Pneumonitis: DISCUSSION
The diagnosis of drug-induced pneumonitis is always difficult, and it may have justified the need for pulmonary biopsy. However, the histologic findings are rarely specific. In our patient, the variations of cellular data obtained by BAL after resumption of treatment with the drug are of diagnostic interest as it was found that lymphocytosis and inversion of the lymphocyte subset ratio paralleled the administration of propranolol and disappeared after withdrawal of the drug. The results of the LMI test, described herein, would appear to help both in the diagnosis of the disease and in understanding its pathogenesis. Various reports have drawn attention to the positive results of this test in different cases of drug-related pneumonitis such as those due to amiodarone, nitrofurantoin, gold salts or methotrexate.
The direct migration inhibition test in the presence of the suspected antigen (drug) was used in these experiments in preference to the indirect method, both because it is more sensitive” but also because it permits the use of a wide range of in vitrv drug concentrations. By cell mixing experiments it was shown that a leukocyte migration inhibitory factor was released only when the patients lymphocytes were present during culture with propranolol. eriacta tablets
The use of a wide range of drug concentrations showed clearly the existence of optimal drug concentrations at which the inhibitory factor appeared, the maximal effect being at 10″3 and 10″* jigfail (3.38 x 10 ® and 3.38 x 10″8 M) and at 36 h of culture. The slight decrease of inhibition at 60 hs suggests that the latter was a dynamic phenomenon.
The patients granulocytes, alone or mixed with normal lymphocytes, failed to develop migration inhibition when cultured with drug over a wide range of drug concentrations (Fig 1), suggesting that in this case at least LMI cannot be attributed to formation of antigen-antibody complexes by drug with antibody-fixed on leukocyte Fc receptors.
The positive LMI test in the patient and the lack of LMI in leukocyte suspensions of two subjects treated with propranolol but without pneumonitis would indicate that the appearance of LMI at low drug concentrations is associated with the presence of the drug-related pneumonitis. This association leads to the hypothesis that the cellular immune response to the drug might itself play a part in the pathogenesis of the lung disorder. The LIF production has also been observed in well-established cases of hypersensitivity pneumonitis such as that due to beryllium.
Finally, the clinical impression that propranolol-related interstitial pneumonitis could be due to an immunologic hypersensitivity mechanism would appear to be confirmed by our data. Since lympholane release is primarily a T-cell (unction, cell-mediated immune phenomena may play a role in the pathogenesis of this disease. Viagra Professional