Abstract
The anti-helminthic drug levamisole hydrochloride has been reported to stimulate immune responses in humans and experimental animals. We have investigated levamisole effects on human leukocyte locomotion in vitro in studies of neutrophils and mononuclear cells from normal adults, from patients with Chediak-Higashi disease and from patients with the syndrome of hyperimmunoglobulin E, recurrent pyogenic infections, and defective leukocyte chemotaxis. Directed migration (chemotaxis) of neutrophils and mononuclear cells from normal adults and from the hyperimmunoglobulin E syndrome patients, but not from Chediak-Higashi patients, were stimulated by levamisole at concentrations of 0.01-1.0 micronM, with stimulation observed most consistently at 0.1 micronM. These concentrations of drug also increased cyclic GMP levels in mononuclear cells and enhanced hexose monophosphate shunt activity in neutrophils, but did not alter chemotactic factor-induced changes in the surface charge of neutrophils. Other concentrations of levamisole did not affect leukocyte locomotion except for a high concentration (5.0 mM) which stimulated both random and directed leukocyte migration. When patients with the hyperimmunoglobulin E syndrome took levamisole by mouth, the abnormal chemotactic responses of their neutrophils were significantly improved towards normal. These studies are the first to show pharmacologic improvement of in vitro leukocyte locomotion in patients in whom recurrent infections have been attributed to a defect of this leukocyte function.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson R., Glover A., Koornhof H. J., Rabson A. R. In vitro stimulation of neutrophil motility by levamisole: maintenance of cgmp levels in chemotactically stimulated levamisole-treated neutrophils. J Immunol. 1976 Aug;117(2):428–432. [PubMed] [Google Scholar]
- Blume R. S., Wolff S. M. The Chediak-Higashi syndrome: studies in four patients and a review of the literature. Medicine (Baltimore) 1972 Jul;51(4):247–280. [PubMed] [Google Scholar]
- Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
- Church J. A., Frenkel L. D., Wright D. G., Bellanti J. A. T lymphocyte dysfunction, hyperimmunoglobulinemia E, recurrent bacterial infections, and defective neutrophil chemotaxis in a Negro child. J Pediatr. 1976 Jun;88(6):982–985. doi: 10.1016/s0022-3476(76)81056-6. [DOI] [PubMed] [Google Scholar]
- Clark R. A., Gallin J. I., Kaplan A. P. The selective eosinophil chemotactic activity of histamine. J Exp Med. 1975 Dec 1;142(6):1462–1476. doi: 10.1084/jem.142.6.1462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark R. A., Kimball H. R. Defective granulocyte chemotaxis in the Chediak-Higashi syndrome. J Clin Invest. 1971 Dec;50(12):2645–2652. doi: 10.1172/JCI106765. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark R. A., Root R. K., Kimball H. R., Kirkpatrick C. H. Defective neutrophil chemotaxis and cellular immunity in a child with recurrent infections. Ann Intern Med. 1973 Apr;78(4):515–519. doi: 10.7326/0003-4819-78-4-515. [DOI] [PubMed] [Google Scholar]
- Copeland D., Stewart T., Harris J. Effect of levamisole (NSC-177023) on in vitro human lymphocyte transformation. Cancer Chemother Rep. 1974 Mar-Apr;58(2):167–170. [PubMed] [Google Scholar]
- De Cree J., Verhaegen H., De Cock W., Vanheule R., Brugmans J., Schuermans V. Letter: Impaired neutrophil phagocytosis. Lancet. 1974 Aug 3;2(7875):294–295. doi: 10.1016/s0140-6736(74)91464-0. [DOI] [PubMed] [Google Scholar]
- Forsyth B. A. The anthelmintic activity of the optical isomers of tetramisole in sheep and cattle. Aust Vet J. 1968 Sep;44(9):395–400. doi: 10.1111/j.1751-0813.1968.tb09128.x. [DOI] [PubMed] [Google Scholar]
- Gallin J. I., Clark R. A., Kimball H. R. Granulocyte chemotaxis: an improved in vitro assay employing 51 Cr-labeled granulocytes. J Immunol. 1973 Jan;110(1):233–240. [PubMed] [Google Scholar]
- Gallin J. I., Durocher J. R., Kaplan A. P. Interaction of leukocyte chemotactic factors with the cell surface. I. Chemotactic factor-induced changes in human granulocyte surface charge. J Clin Invest. 1975 May;55(5):967–974. doi: 10.1172/JCI108026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gallin J. I., Klimerman J. A., Padgett G. A., Wolff S. M. Defective mononuclear leukocyte chemotaxis in the Chediak-Higashi syndrome of humans, mink, and cattle. Blood. 1975 Jun;45(6):863–870. [PubMed] [Google Scholar]
- Gallin J. I., Rosenthal A. S. The regulatory role of divalent cations in human granulocyte chemotaxis. Evidence for an association between calcium exchanges and microtubule assembly. J Cell Biol. 1974 Sep;62(3):594–609. doi: 10.1083/jcb.62.3.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gallin J. I., Wolff S. M. Leucocyte chemotaxis: physiological considerations and abnormalities. Clin Haematol. 1975 Oct;4(3):567–607. [PubMed] [Google Scholar]
- Gatti F., Krubwa F., Vandepitte J., Thienpont D. Control of intestinal nematodes in African schoolchildren by the trimestrial administration of levamisole. Ann Soc Belg Med Trop. 1972;52(1):19–31. [PubMed] [Google Scholar]
- Goetzl E. J., Wasserman S. I., Gigli I., Austen K. F. Enhancement of random migration and chemotactic response of human leukocytes by ascorbic acid. J Clin Invest. 1974 Mar;53(3):813–818. doi: 10.1172/JCI107620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hadden J. W., Coffey R. G., Hadden E. M., Lopez-Corrales E., Sunshine G. H. Effects of levamisole and imidazole on lymphocyte proliferation and cyclic nucleotide levels. Cell Immunol. 1975 Nov;20(1):98–103. doi: 10.1016/0008-8749(75)90088-x. [DOI] [PubMed] [Google Scholar]
- Hill H. R., Ochs H. D., Quie P. G., Clark R. A., Pabst H. F., Klebanoff S. J., Wedgwood R. J. Defect in neutrophil granulocyte chemotaxis in Job's syndrome of recurrent "cold" staphylococcal abscesses. Lancet. 1974 Sep 14;2(7881):617–619. doi: 10.1016/s0140-6736(74)91942-4. [DOI] [PubMed] [Google Scholar]
- Hoebeke J., Franchi G. Influence of tetramisole and its optical isomers on the mononuclear phagocytic system. Effect on carbon clearance in mice. J Reticuloendothel Soc. 1973 Sep;14(3):317–323. [PubMed] [Google Scholar]
- Kint A., Verlinden L. Letter: Levamisole for recurrent herpes labialis. N Engl J Med. 1974 Aug 8;291(6):308–308. doi: 10.1056/NEJM197408082910614. [DOI] [PubMed] [Google Scholar]
- Mickenberg I. D., Root R. K., Wolff S. M. Leukocytic function in hypogammaglobulinemia. J Clin Invest. 1970 Aug;49(8):1528–1538. doi: 10.1172/JCI106370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oliveira Lima A., Javierre M. Q., Dias da Silva W., Sette Camara D. Immunological phagocytosis: effect of drugs on phosphodiesterase activity. Experientia. 1974 Aug 15;30(8):945–946. doi: 10.1007/BF01938377. [DOI] [PubMed] [Google Scholar]
- Pabst H. F., Crawford J. L-tetramisole. Enhancement of human lymphocyte response to antigen. Clin Exp Immunol. 1975 Sep;21(3):468–473. [PMC free article] [PubMed] [Google Scholar]
- Pike M. C., Snyderman R. Augmentation of human monocyte chemotactic response by levamisole. Nature. 1976 May 13;261(5556):136–137. doi: 10.1038/261136a0. [DOI] [PubMed] [Google Scholar]
- Sandler J. A., Gallin J. I., Vaughan M. Effects of serotonin, carbamylcholine, and ascorbic acid on leukocyte cyclic GMP and chemotaxis. J Cell Biol. 1975 Nov;67(2PT1):480–484. doi: 10.1083/jcb.67.2.480. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmidt M. E., Douglas S. D. Effects of levamisole on human monocyte function and immunoprotein receptors. Clin Immunol Immunopathol. 1976 Nov;6(3):299–305. doi: 10.1016/0090-1229(76)90082-9. [DOI] [PubMed] [Google Scholar]
- Snyderman R., Altman L. C., Hausman M. S., Mergenhagen S. E. Human mononuclear leukocyte chemotaxis: a quantitative assay for humoral and cellular chemotactic factors. J Immunol. 1972 Mar;108(3):857–860. [PubMed] [Google Scholar]
- Steiner A. L., Parker C. W., Kipnis D. M. Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides. J Biol Chem. 1972 Feb 25;247(4):1106–1113. [PubMed] [Google Scholar]
- Symoens J., Brugmans J. Letter: Treatment of recurrent aphthous stomatitis and herpes with levamisole. Br Med J. 1974 Dec 7;4(5944):592–592. doi: 10.1136/bmj.4.5944.592. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thienpont D., Brugmans J., Abadi K., Tanamal S. Tetramisole in the treatment of nematode infections in man. Am J Trop Med Hyg. 1969 Jul;18(4):520–525. doi: 10.4269/ajtmh.1969.18.520. [DOI] [PubMed] [Google Scholar]
- Tripodi D., Parks L. C., Brugmans J. Drug-induced restoration of cutaneous delayed hypersensitivity in anergic patients with cancer. N Engl J Med. 1973 Aug 16;289(7):354–357. doi: 10.1056/NEJM197308162890707. [DOI] [PubMed] [Google Scholar]
- Van Scoy R. E., Hill H. R., Ritts R. E., Quie P. G. Familial neutrophil chemotaxis defect, recurrent bacterial infections, mucocutaneous candidiasis, and hyperimmunoglobulinemia E. Ann Intern Med. 1975 Jun;82(6):766–771. doi: 10.7326/0003-4819-82-6-766. [DOI] [PubMed] [Google Scholar]
- Wachi K. K., Kimura L. H., Perreira S., Hokama Y., Perri S., Palumbo N. Effect of levamisole and C-reactive protein on mitogen-stimulated lymphocytes in vitro. Res Commun Chem Pathol Pharmacol. 1974 Aug;8(4):681–696. [PubMed] [Google Scholar]
- Woods W. A., Siegel M. J., Chirigos M. A. In vitro stimulation of spleen cell cultures by poly I: poly C and levamisole. Cell Immunol. 1974 Nov;14(2):327–331. doi: 10.1016/0008-8749(74)90217-2. [DOI] [PubMed] [Google Scholar]
- Zigmond S. H., Hirsch J. G. Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor. J Exp Med. 1973 Feb 1;137(2):387–410. doi: 10.1084/jem.137.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]