Skip to main content
PMC home page
Clinical and Diagnostic Laboratory Immunology logoLink to Clinical and Diagnostic Laboratory Immunology
. 1995 Nov;2(6):766–769. doi: 10.1128/cdli.2.6.766-769.1995

Alterations in peripheral blood mononuclear cell cytokine production in response to phytohemagglutinin in multiple sclerosis patients.

B Crucian 1, P Dunne 1, H Friedman 1, R Ragsdale 1, S Pross 1, R Widen 1
PMCID: PMC170236  PMID: 8574845

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS). The disease is characterized by inflammatory lesions in the white matter of the CNS, consisting of a specific immune response to the myelin sheath. We investigated peripheral blood mononuclear cell (PBMC) cytokine production by enzyme-linked immunosorbent assays of 21 MS patients and 19 age-matched normal controls in response to the T-cell mitogen phytohemagglutinin (PHA). Peripheral blood mononuclear cells were cultured in medium alone or in medium with 5 micrograms of PHA per ml for 48 h, and culture supernatants were collected for analysis. Cytokines selected for study were interleukin-10 (IL-10), gamma interferon (IFN-gamma), IL-2, and IL-4. All cytokine activities described were expressed as concentrations per 500,000 cells. We found that 48% (10 of 21) of the MS patients produced small but detectable levels of IL-10 in medium alone, compared with 26% (5 of 18) of the controls. We found that the MS patients produced significantly higher quantities of IL-10 protein than the controls in response to PHA (mean supernatant concentrations of IL-10 for patients and controls, 421 and 204 pg/ml, respectively [P < 0.05]). No significant differences were detected in the production of IL-2, IFN-gamma, and IL-4 between patients and controls in response to PHA, although patients appeared to display a trend toward decreased production of IFN-gamma.

Full Text

The Full Text of this article is available as a PDF (238.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allegretta M., Nicklas J. A., Sriram S., Albertini R. J. T cells responsive to myelin basic protein in patients with multiple sclerosis. Science. 1990 Feb 9;247(4943):718–721. doi: 10.1126/science.1689076. [DOI] [PubMed] [Google Scholar]
  2. Ando D. G., Clayton J., Kono D., Urban J. L., Sercarz E. E. Encephalitogenic T cells in the B10.PL model of experimental allergic encephalomyelitis (EAE) are of the Th-1 lymphokine subtype. Cell Immunol. 1989 Nov;124(1):132–143. doi: 10.1016/0008-8749(89)90117-2. [DOI] [PubMed] [Google Scholar]
  3. Chen Y., Kuchroo V. K., Inobe J., Hafler D. A., Weiner H. L. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science. 1994 Aug 26;265(5176):1237–1240. doi: 10.1126/science.7520605. [DOI] [PubMed] [Google Scholar]
  4. Correale J., Gilmore W., McMillan M., Li S., McCarthy K., Le T., Weiner L. P. Patterns of cytokine secretion by autoreactive proteolipid protein-specific T cell clones during the course of multiple sclerosis. J Immunol. 1995 Mar 15;154(6):2959–2968. [PubMed] [Google Scholar]
  5. Crucian B., Dunne P., Friedman H., Ragsdale R., Pross S., Widen R. Alterations in levels of CD28-/CD8+ suppressor cell precursor and CD45RO+/CD4+ memory T lymphocytes in the peripheral blood of multiple sclerosis patients. Clin Diagn Lab Immunol. 1995 Mar;2(2):249–252. doi: 10.1128/cdli.2.2.249-252.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dore-Duffy P., Donovan C., Todd R. F., 3rd Expression of monocyte activation antigen Mo3 on the surface of peripheral blood monocytes from patients with multiple sclerosis. Neurology. 1992 Aug;42(8):1609–1614. doi: 10.1212/wnl.42.8.1609. [DOI] [PubMed] [Google Scholar]
  7. Gambi D., Porrini A. M., Giampietro A., Macor S. CD21+ (B2 antigen+) cell decrement and CD4+CD29+ (helper-inducer) cell increment suggest an activation of cell immune reactivity in multiple sclerosis. J Neuroimmunol. 1991 Aug;33(2):97–102. doi: 10.1016/0165-5728(91)90053-a. [DOI] [PubMed] [Google Scholar]
  8. Hafler D. A., Weiner H. L. MS: a CNS and systemic autoimmune disease. Immunol Today. 1989 Mar;10(3):104–107. doi: 10.1016/0167-5699(89)90236-3. [DOI] [PubMed] [Google Scholar]
  9. Hauser S. L., Bhan A. K., Gilles F., Kemp M., Kerr C., Weiner H. L. Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions. Ann Neurol. 1986 Jun;19(6):578–587. doi: 10.1002/ana.410190610. [DOI] [PubMed] [Google Scholar]
  10. Imamura K., Suzumura A., Hayashi F., Marunouchi T. Cytokine production by peripheral blood monocytes/macrophages in multiple sclerosis patients. Acta Neurol Scand. 1993 Apr;87(4):281–285. doi: 10.1111/j.1600-0404.1993.tb05508.x. [DOI] [PubMed] [Google Scholar]
  11. Kennedy M. K., Torrance D. S., Picha K. S., Mohler K. M. Analysis of cytokine mRNA expression in the central nervous system of mice with experimental autoimmune encephalomyelitis reveals that IL-10 mRNA expression correlates with recovery. J Immunol. 1992 Oct 1;149(7):2496–2505. [PubMed] [Google Scholar]
  12. Khoury S. J., Hancock W. W., Weiner H. L. Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain. J Exp Med. 1992 Nov 1;176(5):1355–1364. doi: 10.1084/jem.176.5.1355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kurtzke J. F. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444–1452. doi: 10.1212/wnl.33.11.1444. [DOI] [PubMed] [Google Scholar]
  14. Liblau R. S., Singer S. M., McDevitt H. O. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol Today. 1995 Jan;16(1):34–38. doi: 10.1016/0167-5699(95)80068-9. [DOI] [PubMed] [Google Scholar]
  15. Maimone D., Reder A. T., Gregory S. T cell lymphokine-induced secretion of cytokines by monocytes from patients with multiple sclerosis. Cell Immunol. 1993 Jan;146(1):96–106. doi: 10.1006/cimm.1993.1009. [DOI] [PubMed] [Google Scholar]
  16. Miller A., al-Sabbagh A., Santos L. M., Das M. P., Weiner H. L. Epitopes of myelin basic protein that trigger TGF-beta release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression. J Immunol. 1993 Dec 15;151(12):7307–7315. [PubMed] [Google Scholar]
  17. Navikas V., Link J., Palasik W., Söderström M., Fredrikson S., Olsson T., Link H. Increased mRNA expression of IL-10 in mononuclear cells in multiple sclerosis and optic neuritis. Scand J Immunol. 1995 Feb;41(2):171–178. doi: 10.1111/j.1365-3083.1995.tb03550.x. [DOI] [PubMed] [Google Scholar]
  18. Noronha A., Toscas A., Jensen M. A. Contrasting effects of alpha, beta, and gamma interferons on nonspecific suppressor function in multiple sclerosis. Ann Neurol. 1992 Jan;31(1):103–106. doi: 10.1002/ana.410310119. [DOI] [PubMed] [Google Scholar]
  19. Olsson T., Sun J., Hillert J., Höjeberg B., Ekre H. P., Andersson G., Olerup O., Link H. Increased numbers of T cells recognizing multiple myelin basic protein epitopes in multiple sclerosis. Eur J Immunol. 1992 Apr;22(4):1083–1087. doi: 10.1002/eji.1830220431. [DOI] [PubMed] [Google Scholar]
  20. Porrini A. M., Gambi D., Malatesta G. Memory and naive CD4+ lymphocytes in multiple sclerosis. J Neurol. 1992 Oct;239(8):437–440. doi: 10.1007/BF00856808. [DOI] [PubMed] [Google Scholar]
  21. Powrie F., Coffman R. L. Cytokine regulation of T-cell function: potential for therapeutic intervention. Immunol Today. 1993 Jun;14(6):270–274. doi: 10.1016/0167-5699(93)90044-L. [DOI] [PubMed] [Google Scholar]
  22. Rohowsky-Kochan C., Eiman D., Troiano R., Bansil S., Oleske J., Denny T., Cook S. D. Decreased suppressor-inducer T lymphocytes in multiple sclerosis and other neurological diseases. J Neuroimmunol. 1990 Jul;28(2):161–166. doi: 10.1016/0165-5728(90)90030-q. [DOI] [PubMed] [Google Scholar]
  23. Romagnani S. Induction of TH1 and TH2 responses: a key role for the 'natural' immune response? Immunol Today. 1992 Oct;13(10):379–381. doi: 10.1016/0167-5699(92)90083-J. [DOI] [PubMed] [Google Scholar]
  24. SCHUMACHER G. A., BEEBE G., KIBLER R. F., KURLAND L. T., KURTZKE J. F., MCDOWELL F., NAGLER B., SIBLEY W. A., TOURTELLOTTE W. W., WILLMON T. L. PROBLEMS OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS: REPORT BY THE PANEL ON THE EVALUATION OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS. Ann N Y Acad Sci. 1965 Mar 31;122:552–568. doi: 10.1111/j.1749-6632.1965.tb20235.x. [DOI] [PubMed] [Google Scholar]
  25. Salvetti M., Ristori G., D'Amato M., Buttinelli C., Falcone M., Fieschi C., Wekerle H., Pozzilli C. Predominant and stable T cell responses to regions of myelin basic protein can be detected in individual patients with multiple sclerosis. Eur J Immunol. 1993 Jun;23(6):1232–1239. doi: 10.1002/eji.1830230606. [DOI] [PubMed] [Google Scholar]
  26. Sedgwick J. D., MacPhee I. A., Puklavec M. Isolation of encephalitogenic CD4+ T cell clones in the rat. Cloning methodology and interferon-gamma secretion. J Immunol Methods. 1989 Jul 26;121(2):185–196. doi: 10.1016/0022-1759(89)90159-2. [DOI] [PubMed] [Google Scholar]
  27. Steinman L. Autoimmune disease. Sci Am. 1993 Sep;269(3):106–114. doi: 10.1038/scientificamerican0993-106. [DOI] [PubMed] [Google Scholar]
  28. Söderström M., Link H., Sun J. B., Fredrikson S., Kostulas V., Höjeberg B., Li B. L., Olsson T. T cells recognizing multiple peptides of myelin basic protein are found in blood and enriched in cerebrospinal fluid in optic neuritis and multiple sclerosis. Scand J Immunol. 1993 Mar;37(3):355–368. doi: 10.1111/j.1365-3083.1993.tb02565.x. [DOI] [PubMed] [Google Scholar]
  29. Yssel H., De Waal Malefyt R., Roncarolo M. G., Abrams J. S., Lahesmaa R., Spits H., de Vries J. E. IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T cells. J Immunol. 1992 Oct 1;149(7):2378–2384. [PubMed] [Google Scholar]
  30. Zhang Y., Burger D., Saruhan G., Jeannet M., Steck A. J. The T-lymphocyte response against myelin-associated glycoprotein and myelin basic protein in patients with multiple sclerosis. Neurology. 1993 Feb;43(2):403–407. doi: 10.1212/wnl.43.2.403. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Diagnostic Laboratory Immunology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES