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Prevention of recurrences in frequently relapsing herpes labialis with thymopentin a randomized double-blind placebo-controlled multicenter study

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Summary

The present randomized, placebo-controlled double-blind multicenter study included a population of 36 subjects with frequent recurrences (at least once a month) of herpes labialis. Most of the patients had failed to respond adequately to previous treatment with other therapeutic tools, including acyclovir. Either 50 mg of thymopentin or of placebo was administered 3 times a week, by the subcutaneous route, for 6 weeks. Subsequently, the patients were observed for nearly 6 months on the average. The results achieved with thymopentin for the individual parameters were significantly superior to those obtained with placebo; thus significant improvement was seen in patients on thymopentin in the duration of the longest symptomfree period (prolonged from 2.1 weeks to 20.9 weeks, p = 0.000), in the number of relapses (reduced from 1.6 to 0.4 episodes/month, p = 0.001), and in the total duration of herpes symptoms per month (shortened from 2.0 to 0.3 weeks, p = 0.000). Placebo treatment also resulted in considerable improvement (p < 0.05 or 0.01), but was significantly inferior to the improvement obtained with thymopentin. The longest symptomfree period in the placebo group was prolonged from 2.4 to 11.2 weeks. The number of relapses per month was reduced from 1.4 to 0.8, and the total duration of herpes symptoms per month from 2 to 0.9 weeks. The results of intergroup analyses, in which the observed parameters and the improvement achieved in either group were compared, significantly favored thymopentin treatment. The effect of thymopentin was in all but one parameters superior to that of placebo and highly significant (p < 0.01).

Résumé

La présente étude multicentrique randomisée, contrôlée avec placebo et á double insu, portait sur un groupe de 36 sujets souffrant de récidives fréquentes (une fois par mois au moins) d’herpès labial. La plupart des patients n’avaient pas suffisamment réagi à un traitement antérieur par d’autres thérapeutiques, y compris l’acyclovir. Pendant 6 semaines et à raison de trois fois par semaine, on leur a administré par voie sous-cutanée un placebo ou 50 mg de thymopentine. Par la suite, les patients ont été observés pendant une moyenne de 6 mois. Les résultats obtenus pour les divers paramètres grâce à la thymopentine étaient significativement supérieurs à ceux sous placebo; ainsi on a observé sous thymopentine une amélioration significative en ce qui concerne la durée de la période sans symptômes la plus longue (qui a passé de 2,1 semaines à 20,9 semaines, p = 0,000), en ce qui concerne le nombre de récidives (réduites de 1,6 épisode par mois à 0,4 épisode par mois, p = 0,001) et en ce qui concerne la durée totale de la Symptomatologie herpétique par mois (qui a baissé de 2,0 semaines à 0,3 semaines, p = 0,000). Le traitement placebo a également été suivi d’une amélioration considérable (p < 0,05 ou 0,01) mais significativement inférieure à celle sous thymopentine. Dans le groupe placebo, la période sans symptômes la plus longue a été prolongée de 2,4 semaines à 11,2 semaines. Le nombre de récidives par mois a diminué de 1,4 à 0,8 et la durée totale de la Symptomatologie herpétique par mois a diminué de 2 à 0,9 semaines. Les résultats des analyses inter-grou-pes comparant les paramètres observés et l’amélioration obtenue dans chaque groupe sont en faveur de la thymopentine et ceci de manière significative. L’effet de la thymopentine est supérieur à celui du placebo pour tous les paramètres à l’exception d’un seul et il est hautement significatif (p < 0,01).

Zusammenfassung

Die vorliegende randomisierte plazebokontrollierte, multizentrische Doppelblindstudie umfasst ein Patientengut von 36 Probanden mit häufigen Rückfallen (mindestens einmal pro Monat) von Herpes labialis. Die meisten Patienten hatten auf frühere Behandlung mit anderen Mitteln, einschliesslich Acyclovir, nicht angesprochen. Die Probanden wurden 6 Wochen lang entweder mit Thymopentin (50 mg) oder mit Plazebo dreimal wöchentlich subkutan behandelt. Danach folgte eine Beobachtungszeit von durchschnittlich fast 6 Monaten. Die mit Thymopentin für die einzelnen Parameter erzielten Ergebnisse waren den Resultaten mit Plazebo signifikant überlegen. So kam es mit Thymopentin zu signifikant gesteigerter Dauer der längsten symptomfreien Periode (verlängert von 2,1 auf 20,9 Wochen, p = 0,000), zu geringerer Anzahl von Rückfällen (reduziert von 1,6 Episoden pro Monat auf 0,4 Rückfälle pro Monat, p = 0,001), sowie zu verminderter Gesamtdauer der Herpessymptome pro Monat (verkürzt von 2,0 auf 0,3 Wochen, p = 0,000). Auch die Behandlung mit Plazebo führte zu deutlicher Besserung (p < 0,05 oder 0,01), jedoch lag diese signifikant unter den mit Thymopentin erzielten Ergebnissen. Die längste symptomfreie Periode in der Plazebogruppe verlängerte sich von 2,4 auf 11,2 Wochen. Die Anzahl der Rückfälle pro Monat sank von 1,4 auf 0,8 Wochen, und die Gesamtdauer der Herpessym ptome pro Monat ging von 2 auf 0,9 Wochen zurück. Die Ergebnisse der Vergleiche zwischen den Gruppen, wobei die beobachteten Parameter und die in den beiden Gruppen erzielte Besserung in Betracht gezogen wurden, sprach signifikant zugunsten von Thymopentin. Die Wirkung von Thymopentin übertraf das Plazebo in allen Parametern mit nur einer Ausnahme und war hochsignifikant (p < 0,01).

Riassunto

II presente articolo riferisce su uno studio multicentrico, sotto controllo, con placebo e in parallelo effettuato su 36 pazienti con recidive frequenti (almeno una volta al mese) d’herpes labiale. La maggior parte dei soggetti non aveva reagito in modo adeguato ad una terapia précédente con altri medicamenti, aciclovir compreso. Durante sei settimane furono somministrati a questi pazienti, per via sottocutanea, sia 50 mg di thymopentine, sia un placebo, tre volte alla settimana. In seguito, i pazienti furono tenuti sotto controllo durante una media di 6 mesi circa. I risultati ottenuti con la thymopentine erano, per i diversi parametri, significativamente superiori a quelli ottenuti con placebo. Per esempio, si osservò un miglioramento significativo nei pazienti trattati con thymopentine per cio che concerne il periodo di tempo più lungo esente da sintomi (con un prolungamento da 2,1 settimane a 20,9 settimane, p = 0,000), per il numero di recidive (ridotte da 1,6 episodi al mese a 0,4 episodi per la medesima durata, p = 0,001), come pure per ciù che concerne la durata totale della sintomatologia herpetica al mese (diminuzione da 2,0 settimane a 0,3 settimane, p = 0,000). II trattamento a base di placebo ha pure avuto come conseguenza un miglioramento considerevole (p < 0,05 o 0,01), restando perù significativamente inferiore al miglioramento intervenuto dopo terapia con thymopentine. II periodo di tempo più lungo esente da sintomi, nel gruppo con placebo, è stato prolungato da 2,4 settimane a 11,2 settimane. Il numéro délie récidive mensili è diminuito da 1,4 a 0,8 e la durata totale della sintomatologia herpetica al mese si è abbassata da 2 a 0,9 settimane. I risultati delle analisi inter-gruppi ottenuti paragonando i parametri osservati e il miglioramento ottenuto in ogni gruppo hanno messo in evidenza in modo significativo la terapia con thymopentine. La sua azione è stata superiore a quella del placebo in tutti i parametri, ad eccezione di uno ed è stata nettamente significativa (p < 0,01).

Resumen

El presente estudio multicéntrico, randomizado, doble ciego y controlado por placebo comprendió 36 sujetos con frecuentes recurrencias (una vez al mes como minimo) de herpes labial. La mayoría de los pacientes no respondió adecuadamente a un tratamiento anterior con otros agentes terapéeuticos, entre los cuales aciclovir. Se administró timopentina 50 mg o placebo 3 veces a la semana por vía subcutánea, durante 6 semanas. Después de 10 cual se observé a los pacientes durante casi 6 meses por término medio. Los resultados obtenidos con timopentina en los parámetros individuates fueron significativamente superiores a los obtenidos con placebo; asi, se observó una mejoría significative en pacientes con timopentina en la duración del período asintomático més largo (prolongado de 2,1 semanas a 20,9 semanas, p = 0,000), en el número de récidivas (reducido de 1,6 episodios/mes a 0,4 episodios/mes, p = 0,001), y en la duración total de los síntomas de herpes por mes (acortados de 2,0 semanas a 0,3 semanas, p = 0,000). El tratamiento con placebo tuvo asimismo por resultado una majoría considerable (p < 0,05 o 0,01), pero fue significativamente inferior a la mejoría obtenida con timopentina. El período asintomàtico mas largo en el grupo placebo fue prolongado de 2,4 semanas a 11,2 semanas. El número de recaídas/mes se redujo de 1,4 a 0,8 y la duración total de los sintomas de herpes/mes de 2 a 0,9 semanas. Los resultados de los análisis intergrupos, en que se compararon los parámetras observados y la mejoria obtenida en los dos grupos, favorecieron significativamente al tratamiento con timopentina. El efecto de la timopentina fue superior al de placebo y altamente significativo (p < 0,01) en todos los parametras menos en uno.

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References

  1. Juretic, M.: Natural history of herpetic infection. Helv. Paediat. Acta4: 356–368 (1966).

    Google Scholar 

  2. Nahmias, A.J.; Josey, W.E.: Herpes simplex viruses 1 and 2; in Evans, Viral infections of humans. Epidemiology and control; 2nd ed., pp. 351–371 (Plenum Publishing, New York 1983).

    Google Scholar 

  3. Overall, J.C., Jr.: Oral herpes simplex: pathogenesis, clinical and virological course, approach to treatment; in Hooks, Jordan, Viral infections in oral medicine, pp. 53–78 (Elsevier, North Holland, New York 1982).

    Google Scholar 

  4. Overall, J.J.: Dermatologie disease; in Galasso, Merigan, Buchanan, Antiviral agents and viral disease of man; 2nd ed., pp. 247–312 (Rowen Press, New York 1984).

    Google Scholar 

  5. Embil, J.A.; Stephens, R.G.; Manuel, F.R.: Prevalence of recurrent herpes labialis and aphthous ulcers among young adults on six continents. Can. med. Ass. J.11: 627–630 (1975).

    Google Scholar 

  6. Ship, I.I.; Brightman, V.J.; Laster, L.L.: The patient with recurrent aphthous ulcers and the patient with recurrent herpes labialis: a study of two population samples. J. Am. dent. Ass.75: 645–654 (1967).

    PubMed  CAS  Google Scholar 

  7. Ship, I.I.; Morris, A.L.; Durocher, R.T.; Burket, L.W.: Recurrent aphthous ulcerations and recurrent herpes labialis in a professional school population. Oral surg.13: 1191–1202 (1960).

    Article  Google Scholar 

  8. Francis, D.P.; Herrmann, K.L.; MacMahon, J.R.: Nosocomial and maternally acquired herpes virus hominis infections: a report of four fatal cases in neonates. Am. J. Dis. Child.129: 889–893 (1975).

    PubMed  CAS  Google Scholar 

  9. Greenberg, M.S.; Brightman, V.J.; Ship, LI.: Clinical and laboratory differentiation of recurrent intraoral herpes simplex virus infections following fever. J. dent. Res.48: 385–391 (1969).

    PubMed  CAS  Google Scholar 

  10. Gunby, P.: Genital herpes research: many aim to tame Maverick virus. J. Am. med. Ass.250: 2417–2427 (1983).

    Article  CAS  Google Scholar 

  11. Corey, L.: The diagnosis and treatment of genital herpes. J. Am. med. Ass.248: 1041–1049 (1982).

    Article  CAS  Google Scholar 

  12. Stalder, H.: Herpes-Virus-Infektionen bei immun-supprimierten Patienten. Ther. Umschau39: 675–680 (1982).

    CAS  Google Scholar 

  13. Haneke, E.; Bolla, K.; Degreef, H.; Djawari, D.; DeMaubeuge, J.; Molin, L.; Panconesi, E.; Schöpf, E.; Stengel, R.; Stingl, G.; Wolff, K.; Wüthrich, B.: Effect of thymopentin treatment on the relapse rate in frequently relapsing herpes simplex virus infections. Int. J. clin. Pharm. Res.4: 439–443 (1984).

    CAS  Google Scholar 

  14. Djawari, D.; Bolla, K.; Haneke, E.: Behandlung des Herpes simplex recidivans mit Thymopoietin-pentapeptide. Dt. med. Wschr.109: 496–498 (1984).

    CAS  Google Scholar 

  15. Nuss, D.D.; Aeling, J.J.: Herpes simplex: treatment today. Cutis20: 237–241 (1977).

    PubMed  CAS  Google Scholar 

  16. Goldberg, E.H.; Goldstein, G.; Boyse, E.A.; Scheid, M.P.: Effect of the TP-5 analogue of thymopoietin on the rejection of male skin by aged and thymectomized female mice. Immunogenetics13: 201–204 (1981).

    Article  PubMed  CAS  Google Scholar 

  17. Lau, C.Y.; Freestone, J.A.; Goldstein, G.: Effect of thymopoietin pentapeptide on autoimmunity. I. TP-5 suppression of induced erythrocyte autoantibodies in C3H mice. J. Immun.125: 1634–1638 (1980).

    PubMed  CAS  Google Scholar 

  18. Weksler, M.E.; Innes, J.B.; Goldstein, G.: Immunological studies of aging. IV. The contribution of thymic involution to the immune deficiencies of aging mice and reversal with thymopoietin32-36. J. exp. Med.148: 996–1006 (1978).

    Article  PubMed  CAS  Google Scholar 

  19. Sunshine, G.H.; Basch, R.S.; Coffey, R.G.; Cohen, K.W.; Goldstein, G.; Hadden, J.W.: Thymopoietin enhances the allogeneic response and cyclic GMP levels of mouse peripheral thymus-derived lymphocytes. J. Immun.120: 1594–1599 (1978).

    PubMed  CAS  Google Scholar 

  20. Lau, C.Y.; Goldstein, G.: Functional effects of TP-5 on cytotoxic lymphocyte precursor units (CLP-U). I. Enhancement of splenic CLP-U in vitro and in vivo after suboptimal antigenic stimulations. J. Immun.124: 1861–1865 (1980).

    PubMed  CAS  Google Scholar 

  21. Lau, C.Y.; Wang, E.Y.; Goldstein, G.: Effect of thymopoietin pentapeptide on experimental tumors. I. TP-5 relieves immunosuppression in tumor bearing mice. Cell. Immunol.66: 217–232 (1982).

    Article  PubMed  CAS  Google Scholar 

  22. Duchateau, J.; Delespesse, G.; Bolla, K.: Phase variation in the modulation of the human immune response. Immunol. Today4: 213–214 (1983).

    Article  Google Scholar 

  23. Bolla, K.; Duchateau, J.; Delespesse, G.; Servais, G.: Immunomodulation with thymopentin in humans. Int. J. clin. Pharm. Res.4: 431–438 (1984).

    CAS  Google Scholar 

  24. Schooley, R.T.; Hirsch, M.S.; Colvin, R.B.; Cosimi, A.B.; Tolkoff-Rubin, N.E.; McCluskey, R.T.; Burton, R.C.; Russell, P.S.; Herrin, J.T.; Delmonico, F.L.; Giorgi, J.V.; Henle, W.; Rubin, R.H.: Association of herpesvirus infection with T-lym-phocytes-subset alterations, glomerulopathy, and opportunistic infections after renal transplantation. New Engl. J. Med.308: 307–313 (1983).

    PubMed  CAS  Google Scholar 

  25. Rheinherl, E.L.; O’Brien, C; Rosenthal, P.; Schlossman, S.F.: The cellular basis for viral-induced immunodeficiency: analysis by monoclonal antibodies. J. Immun.125: 1269–1274 (1980).

    Google Scholar 

  26. Rinaldo, C.R., Jr.; Carney, W.P.; Richter, B.S.; Black, P.H.; Hirsch, M.S.: Mechanisms of immunosuppression in cytomegaloviral mononucleosis. J. infect. Dis.141: 448–495 (1980).

    Google Scholar 

  27. Mani, R.J.; Niederman, J.C.; Kelleher, J.E.; Dwyer, J.M.; Evans, A.S.; Kantor, E.S.: Depression of cell-mediated immunity during acute infectious mononucleosis. New Engl. J. Med.291: 1149–1153 (1974).

    Google Scholar 

  28. Haynes, B.F.; Scholley, R.T.; Payling-Wright, C.R.; Crouse, J.E.; Dolin, R.; Fauci, A.S.: Emergence of suppressor cells of immunoglobulin synthesis during acute Epstein-Barr virus-induced infectious mononucleosis. J. Immun.123: 2095–2101 (1979).

    PubMed  CAS  Google Scholar 

  29. Tosato, G.; Magrath, I.; Koski, I.; Dooley, N.; Blaese, M.: Activation of suppressor T cells during Epstein-Barr virus-induced infectious mononucleosis. New Engl. J. Med.301: 1133–1137 (1979).

    PubMed  CAS  Google Scholar 

  30. Mascart-Lemone, F.; Huygen, K.; Clumeck, N.; Brenez, D.; Bolla, K.; Duchateau, J.: Stimulation of cellular function by thymopentin (TP-5) in three AIDS patients. Lancetii: 735–736 (1983).

    Article  Google Scholar 

  31. Diezel, W.; Waschke, S.; Forner, K.: Thymopoietin pentapeptide (TP-5) - an inducer of interferon production in human lymphocytes. Biomed. biochem. Acta (in press, 1985).

  32. Rentz, E.; Diezel, W.: Influence of thymic hormones on mitogen-induced interferon production in lymphocytes. I. Augmentation of mitogen-induced immune interferon production by thymosin. Arch. Geschwulstforsch.53: 547–550 (1983).

    PubMed  CAS  Google Scholar 

  33. Cappel, R.; DeCuyper, F.; DeNeef, K.; Bolla, K.: Effect of thymopentin on the mortality and immune response after an experimental herpes simplex infection in mice. Surv. immunol. Res.4: suppl. 1, pp. 48–57 (1985).

    PubMed  CAS  Google Scholar 

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Bolla, K., Djawari, D., Kokoschka, E.M. et al. Prevention of recurrences in frequently relapsing herpes labialis with thymopentin a randomized double-blind placebo-controlled multicenter study. Surv. immunol. Res. 4 (Suppl 1), 37–47 (1985). https://doi.org/10.1007/BF02919055

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