ABSTRACT
Sepsis and septic shock can be caused by Gram-positive and -negative bacteria and other microorganisms. In the case of Gram-negative bacteria, endotoxin, a normal constituent of the bacterial wall, also known as lipopolysaccharide (LPS), has been considered as one of the principal agents causing the undesirable effects in this critical illness. The response to LPS involves a rapid secretion of proinflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, interferon (IFN)-γ and the concomitant induction of anti-inflammatory mediators such as IL-10, transforming growth factor (TGF)-ß or glucocorticoids, which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the main cause of the non-specific humoral and cellular immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that mifepristone (RU486), a known glucocorticoid receptor antagonist, could play an important role in the restoration of both adaptive humoral and cellular immune response in LPS immunosuppressed mice, suggesting the involvement of endogenous glucocorticoids in this phenomenon. On the other hand, using cyclophosphamide and gemcitabine, we demonstrated that regulatory/suppressor CD4(+) CD25(+) forkhead boxP3(+) and GR-1(+) CD11b(+) cells do not play a major role in the establishment or the maintenance of endotoxin tolerance, a central mechanism for inducing an immunosuppression state.
Subject(s)
Mifepristone/administration & dosage , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes/drug effects , Animals , Antigens, CD/biosynthesis , Cyclophosphamide/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Forkhead Transcription Factors/biosynthesis , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Immunosuppression Therapy , Immunosuppressive Agents/administration & dosage , Lipopolysaccharides/administration & dosage , Mice , Mice, Inbred BALB C , Mifepristone/pharmacology , Receptors, Glucocorticoid/antagonists & inhibitors , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/pathology , GemcitabineABSTRACT
An antiserum-agar technique was evaluated as a method for detecting Salmonella typhi in faeces. Thirty-one laboratory strains of S. typhi produced immunoprecipitate haloes during overnight growth on SS agar and blood-agar-base infusion agar (BAB) containing donkey antiserum to a vaccine strain of S. typhi. Other salmonella species sharing O serogroup antigens with S. typhi also produced haloes when streaked in pure culture on SS-antiserum agar but not on BAB-antiserum agar. One hundred and forty-one consecutive faecal specimens were cultured on SS-antiserum agar. Results with this method were concordant with those of established isolation techniques on specimens from six of seven suspected carriers of S. typhi. Ten other salmonellas were isolated from the faecal specimens but only S. javiana, like S. typhi a serogroup-D organism, yielded false-positive haloes on antiserum agar. The antiserum-agar technique offers promise as a means of screening for S. typhi in faecal cultures.
