Int. J. lmmunopharmac., Vol. 8, No. 3, pp, 245-259, 1986. 0192-0561/86 $3.00+ .00 Printed in Great Britain. © 1986 International Society for lmmunopharmacology. IMMUNOPHARMACOLOGICAL EFFECTS OF SACCHAROMYCES BOULARDII IN HEALTHY HUMAN VOLUNTEERS J. A. MACHADO CAETANO, M. T. PARAMI~S, M. J. BABO, A. SANTOS, A. BANDEIRA FERREIRA, A. A. FREITAS, M. R. CLEMENTE COELHO and A. MATTHIOLIMATEUS Serviqo de Imunologia, Faculdade de Ci~ncias M6dicas, Campo de Santana 130, 1100 Lisboa, Portugal (Received 31 July 1985 and in final form 1 August 1985) Abstract -- Investigation of oral administration of Saccharomyces boulardii in healthy volunteers demonstrates several cellular and humoral changes in peripheral blood. Among its effects are the increase of erythrocytes, leucocytes, polymorphs, neutrophils, complement components C3, C5, C3d, serum anticomplementary activity and leucocyte cbemokinesis, specially when autologous serum and antigen have been added to the culture medium and decrease of complement haemolytic activity (CH50, classic and alternative pathways). We have also demonstrated that in vitro S. boulardii was able to activate complement directly, to fix C3b to its surface and that its phagocytosis by mononuclear cells was complement-dependent. The overall changes in serum proteins suggested changes of acute phase proteins typical of an inflammatory process. Furthermore S. boulardii had no mitogenic response of lymphocyte populations. Our results demonstrated that S. boulardii activates the reticuloendothelial system and complement system and suggest that S. boulardii merits therapeutic trial in a variety of clinical situations. Immunological incompetence is very common in medical practice, considering that beyond primary immune deficiencies there are many secondary deficiencies roused not only by infection but also by cancer, aging, surgery, bad nutrition, burns, radiations, chemotherapy and antibiotherapy. The growing number of these situations has justified the research of immunotherapeutic agents which may potentiate the resistance of an incompetent host. BCG strain of Mycobacterium bovis, Coryne- bacterium parvum and different species of Nocardia are some of the most well known agents (Math6, 1973; Halpern, Biozzi, Stiffel & Mouton, 1976, Barot-Ciorbaru, Petit, Chassoux & Salomon, 1981). In recent years several publications refer to the use of products obtained from bacteria, virus and yeasts, in experiments that seek to obtain a non-toxic agent, able to increase natural and/or acquired resistance without side effects. It has already been demonstrated in animal and man that yeasts and their by-products can influence host defences against certain infections and tumours. The action of Zymosan on the complement system has been known for some time (Pillemer, Blum, Lepow, Ross, Todd & Wardlaw, 1954) as well as the fact that some polysaccharides extracted from yeasts stimulate the reticuloendothelial system (R.E.S.) and non specific defences (Riggi & DiLuzio, 1961) against pathogenic agents (Massot, Desconclois & Patte, 1978; Seguela, Massot, Nesson & Patte, 1978; Williams, Cook, Hoffman & DiLuzio, 1978) and tumours (Mansell, DiLuzio, McNamee, Rowden & Proctor, 1976; DiLuzio, McNamee, Browder & Williams, 1978). Unfortunately the use of such yeast by-products in man is limited (Mansell et al., 1976; Kohl, Pickering & DiLuzio, 1979). Some authors tested oral administration of living yeasts in animals (Massot et al., 1978; Seguela et al., 1978) and man (Adam et al., 1976) and referred an anti-infectious protection. Therefore it is of the greatest convenience to try to clarify the effects of these biological agents on specific and non-specific defences in man. With this purpose in mind the immunopharmacological effects of a particular strain of Saccharomyces boulardii were studied in human volunteers who were given the yeast orally. 245