Summary
Using a direct assay of leukocyte migration inhibitory factor (LMIF), cell-mediated immunity to herpes simplex virus (HSV) antigen was measured in patients who had primary and recurrent ocular HSV infections. Those with primary and recurrent epithelial disease had a significantly lower production of LMIF than a control population that had had no herpetic infection for at least a year or longer (P<0.001). On the contrary, patients with deep stromal involvement and anterior uveitis showed significant migration inhibition with HSV antigen, similar to the one found in the healthy control group. The clinical and possible therapeutic implications of these findings are discussed.
Zusammenfassung
Mit Hilfe eines direkten Testes zur Bestimmung des Leukocyten-Migrations-Inhibitions-Faktors (LMIF) wurde die zelluläre Immunität gegen Herpes simplex-Virus (HSV) Antigen bei Patienten mit primärem und rezidivierendem Herpes corneae untersucht. Dabei zeigten Patienten mit primärem oder rezidivierendem epithelialen Befall gegenüber Personen einer Kontrollgruppe, die mindestens für ein Jahr keine Infektion mit HSV durchgemacht hatten, eine signifikant verminderte Produktion von LMIF (P < 0,001). Im Gegensatz dazu war bei Patienten mit schwerer Beteiligung des Hornhautstromas und Iridocyclitis eine signifikante Hemmung der Migration in gleicher Größenordnung wie in der gesunden Kontrollgruppe feststellbar. Die klinischen und möglichen therapeutischen Folgerungen werden diskutiert.
Similar content being viewed by others
References
Allen, D.E., Pinnell, S.R., Tindall, J.P.: Levamisole therapy for recurrent herpes simplex and aphthous stomatitis. American Academy of Dermatology, San Francisco, Dec. 5, 1975
Aston, D.L., Cohen, A., Spindler, M.A.: Herpes virus hominis infection in patients with myeloproliferative and lymphoproliferative disorders. Br. Med. J. 1972 IV, 462–465
Bastian, F.O., Rabson, C.L., Yee, T.S.: Herpes virus hominis: Isolation from human trigeminal ganglia. Science 178, 306–307 (1972)
Braley, A.E.: Experimental herpes simplex: Sanford R. Gifford Lecture. Am. J. Ophthalmol. 35, 1737–1747 (1952)
Centifanto, Y.M., Kaufman, H.E.: The development of tear antibodies and herpes simplex keratitis. In: The secretory immunologic system (D.H. Dayton et al., ed.), pp. 331–340. Bethesda, MD: US. Dept. of Heath Education and Welfare, PHS, NIH 1969
Centifanto, Y.M., Little, J.M., Kaufman, H.E.: The relationship between virus chemotherapy, secretory antibody formation and recurrent herpetic disease. Ann. NY Acad. Sci. 173, 649–654 (1970)
Centifanto, Y.M., Zam, Z.S., McNeill, J.J., Kaufman, H.E.: Leukocyte migration inhibitory factor in HSV infections. Invest. Ophthalmol. Visual Sci. 17, 863–868 (1978)
Colin, J.: L'herpès oculaire. Aspects thérapeutiques. Nouv. Presse Med. 7, 2949–2953 (1978)
Easty, D.L., Maini, R.N., Jones, B.R.: Cellular immunity in herpes simplex keratitis. Trans. Ophthalmol. Soc. UK 93, 171–180 (1973)
Florentin, J., Huchet, R., Bruley-Rosset, M., Halle-Panenko, O., Mathe, G.: Studies on the mechanisms of action of BCG. Cancer Immunol. Immunother. 1, 31–39 (1976)
Friedlaender, M.H., Smolin, G., Okumoto, M.: The treatment of herpetic reinfection with levamisole. Am. J. Ophthalmol. 86, 245–249 (1978)
Fuchs, E.: Über ringförmige und scheibenförmige Keratitis (Keratitis annularis et disciformis). Klin. Monatsbl. Augenheilkd. 39, 513–523 (1901)
Gange, R.W., De Bats, A., Park, J.R., Bradstreet, C.M.P., Rhodes, E.L.: Cellular immunity and circulating antibody to herpes simplex virus in subjects with recurrent herpes simplex lesions and controls as measured by the mixed leukocyte migration inhibition and complement fixation. Br. J. Dermatol. 97, 539–544 (1975)
Glade, P.R., Broder, S.W., Grotsiky, H., Hirschhorn, K.: The use of cultured lymphoid cells as target cells for the detection of migration inhibitory factors. In: In vitro methods in cell-mediated immunity, pp. 307–312. New York: Academic Press 1971
Haahr, S., Rasmussen, L., Merigan, T.C.: Lymphocyte transformation and interferon production in human mononuclear cell microcultures for assay of cellular immunity to herpes simplex virus. Infect. Immun. 14, 47–54 (1976)
Henson, D., Helmsen, R., Becker, K.E., Strano, A.J., Sullivan, M., Harris, D.: Ultrastructural localization of herpes simplex virus antigens on rabbit corneal cells using sheep antihuman IgG antihorse ferritin hybrid antibodies. Invest. Ophthalmol. 13, 819–827 (1974)
Jarisch, R., Sandor, I., Stingl, G., Pehamberger, H., Pichler, W.: Levamisoltherapie bei Neurodermitis atopica (Doppelblindstudie). V. Jahrestagung d. Arbeitsgemeinschaft für Dermatologische Forschung, Frankfurt 1977
Jarisch, R., Sandor, I.: MIF in der Therapiekontrolle von Herpes simplex recidivans: Behandlung mit Levamisole, BCG, Urushiol und Herpes Antigen Vaccine. Arch. Dermatol. Res. 258, 151–159 (1977)
Jarisch, R., Sandor, I., Cerni, C.: Der Leukozytenmigrationshemmtest (LMIT) bei Herpes simplex labialis recidivans. Vergleich der Therapieerfolge mit BCG und Levamisole. Arch. Dermatol. Res. (in press 1979)
Kaufman, H.E., Martola, E.L., Dohlman, C.H.: Herpes simplex treatment with IDU and corticosteroids. Arch. Ophthalmol. 69, 468–472 (1963)
Kaufman, H.E., Varnell, E.D.: Lack of levamisole effect on experimental herpes keratitis. Invest. Ophthalmol. Visual Sci. 16, 1148–1150 (1977)
Knit, A., Verlinden, L.: Levamisole for recurrent herpes labialis. N. Engl. J. Med. 291, 308 (1974)
Lopez, C., O'Reilly, R.J.: Cell-mediated immune responses in recurrent herpes virus infections. I. Lymphocyte proliferation assay. J. Immunol. 118, 895–902 (1977)
Martin, R.G., Dawson, C.R., Jones, P., Togni, B., Lyons, C., Oh, J.O.: Herpes virus in sensory and autonomic ganglia after eye infection—absence of chronic viral shedding. Arch. Ophthalmol. 95, 2053–2056 (1977)
Metcalf, J.F., McNeill, J.J., Kaufman, H.E.: Experimental disciform edema and necrotizing keratitis in the rabbit. Invest. Ophthalmol. 15, 979–985 (1976)
Metcalf, J.F., Kaufman, H.E.: Herpetic stromal keratitis—evidence for cell-mediated immunopathogenesis. Am. J. Ophthalmol. 82, 827–833 (1976)
Metcalf, J.F., Helmsen, R.: Immunoelectron microscopic localization of herpes simplex virus antigens in rabbit cornea with antihuman IgG-antiferritin hybrid antibodies. Invest. Ophthalmol. Visual Sci. 16, 779–786 (1977)
Montgomerie, J.Z., Croxon, M.C., Becroft, D.M.O., Doak, P.B., North, J.D.K.: Herpes simplex virus infection after renal transplantation. Lancet, 1969 II, 867–871
Nesburn, A.B., Cook, M.L., Stevens, J.G.: Latent herpes simplex virus: Isolation from rabbit trigeminal ganglia between disease episodes. Arch. Ophthalmol. 88, 412–417 (1972)
O'Reilly, R.J., Chibbaro, A., Anger, E., Lopez, C.: Cell-mediated immune responses in patients with recurrent herpes simplex infections. II. Infection-associated deficiency of lymphokine production in patients with recurrent herpes labialis or herpes progenitalis. J. Immunol. 118, 1095–1102 (1977)
Pier, F.D., Smith, T.F., Andersen, C.F., Webel, M.L., Tasewell, H.F.: Herpes virus in renal transplant patients. Transplantation 16, 489–495 (1973)
Plummer, G.: Isolation of herpes viruses from trigeminal ganglia of man, monkeys and cats. J. Infect. Dis. 128, 345–348 (1973)
Rasmussen, L.E., Jordan, G.W., Stevens, D.A., Merigan, T.C.: Lymphocyte interferon production and transformation after herpes simplex infections in humans. J. Immunol. 112, 728–736 (1974)
Raud, K.H., Rasmussen, L.E., Pollard, R.B., Arvin, A., Merigan, T.C.: Cellular immunity and herpes virus infections in cardiac-transplant patients. N. Engl. J. Med. 296, 1372–1377 (1977)
Rosenberg, G.L., Snyderman, R., Notkins, A.L.: Production of chemotactic factor and lymphotoxin by human leukocytes stimulated with herpes simplex virus. Infect. Immun. 10, 111–115 (1974)
Russel, A.S., Percy, J.S., Kovithavongs, T.: Cell mediated immunity to herpes simplex in humans. Lymphocyte cytotoxicity measured by 51 Cr release from infected cells. Infect. Immun. 11, 355–362 (1975)
Russel, A.S., Konsei, J., Lao, V.S.: Cell mediated immunity to herpes simplex in man. IV. A correlation of lymphocyte stimulation and inhibition of leukocyte migration. J. Immunol. Methods 9, 273–277 (1976)
Sery, T.W., Nagy, R.M.: Cellular reaction in experimental herpetic disciform keratitis. Am. J. Ophthalmol. 83, 675–680 (1977)
Sher, N.A., Poplack, D.G., Blaese, R.M., Brown, T.M., Chaparas, S.C.: Effect of Corynebacterium parvum, methanol-extraction residue of BCG and levamisole on macrophage random migration, chemotaxis and periocytosis. J. Natl. Cancer Inst. 58, 1753–1757 (1977)
Smolin, G., Tabbara, K., Okumoto, M.: Guinea pig herpes simplex keratitis treated with a lymphocyte extract. Am. J. Ophthalmol. 78, 921–925 (1974)
Smolin, G., Okumoto, M., Belfort, R., Jr.: The treatment of experimental herpetic keratitis with BCG. Can. J. Ophthalmol. 10, 385–390 (1975)
Smolin, G., Okumoto, M., Friedlaender, M.: Treatment of herpes simplex keratitis with levamisole. Arch. Ophthalmol. 96, 1078–1081 (1978)
Steele, R.W., Vincent, M.M., Hensen, S.A., Fucillo, D.A., Chapa, L.S., Canales, L.: Cellular immune responses to herpes simplex virus type 1 in recurrent labialis: In vitro blastogenesis and cytotoxicity to infected cell lines. J. Infect. Dis. 131, 528–534 (1975)
St. Geme, J.W., Prince, J.T., Burke, B.A., Good, R.A., Krivit, W.: Impaired cellular resistance to herpes simplex virus in Wiskott-Aldrich syndrome. N. Engl. J. Med. 273, 229–234 (1965)
Sundmacher, R.: Herpestherapie und -prophylaxe. I. Versuch einer kritischen Wertung. Klin. Monatsbl. Augenheilkd. 169, 308–325 (1976)
Swyers, J.S., Lausch, R.N., Kaufman, H.E.: Corneal hypersensitivity to herpes simplex. Br. J. Ophthalmol. 51, 843–846 (1967)
Symoens, J., Brugmans, J.: Treatment of recurrent aphthous stomatitis and herpes with levamisole. Br. Med. J. 1974 IV, 592–593
Thong, Y.H., Vincent, M.M., Hensen, S.A., Fucillo, D.A., Rola-Pleszczynski, M., Bellanti, J.A.: Depressed specific cell mediated immunity to herpes simplex virus type 1 in patients with recurrent herpes labialis. Infect. Immun. 12, 76–80 (1975)
Tokumary, T.Y., Shimizu, Y., Sabety, Y.: Herpetic epithelial keratitis: A radioassay evaluation of the host's humoral and cellular responsiveness. Ophthalmic. Res. 7, 345–353 (1975)
Verhaegen, H., Decree, J., De Cock, W.: Levamisole and the immune response. N. Engl. J. Med. 289, 1148–1149 (1974)
Williams, L.E., Nesburn, A.B., Kaufman, H.E.: Experimental induction of disciform keratitis. Arch. Ophthalmol. 73, 112–114 (1965)
Wilton, J.M.A., Ivanyi, L., Lehner, T.: Cell mediated immunity in herpes virus hominis infections. Br. Med. J. 1972 I, 723–726
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Grabner, G., Jarisch, R. Leukocyte migration inhibitory factor in primary and recurrent ocular infections by herpes simplex-virus. Albrecht von Graefes Arch. Klin. Ophthalmol. 211, 85–93 (1979). https://doi.org/10.1007/BF00414656
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00414656