[Experimental evaluation of antibiotics as immunomodulators].
Since the pioneer work by Metchnikoff, the goal of cooperation between therapeutics and the host defence system (HDS) has been sought after. This area of research received less attention after the introduction of antibiotics. Although, the predictive efficacy of antibacterial agents (ABA) is still evaluated in terms of MICs, MBCs, and pharmacokinetics, much evidence derived from clinical studies underlines the need for synergy between HDS and these drugs to obtain optimal therapeutic efficacy. The analysis of the immunomodifying properties of ABA has come under intense study. The majority of ABA does not substantially affect the functioning of the immune system at least in vivo, despite in-vitro observations of enhancement/inhibition of various immune parameters by some cephalosporins, macrolides, cyclins, aminoglycosides, etc. By contrast, chloramphenicol, sulphonamides and various beta-lactams may be responsible for drug-induced neutropenia whereas macrolides and quinolones, due to their high phagocytic uptake, synergize with phagocytes to destroy intracellular pathogens. Recently, the concept of Biological Response Modifier (BRM)-antibiotics has come under the limelight with the introduction of cefodizime, a new parenteral cephalosporin, which seems to be endowed with immunomodulating properties. This latter aspect has been demonstrated in vitro (potentiation of the phagocyte antimicrobial activity), ex vivo in immunocompromised animals and humans (restoration of various immune parameters) and in vivo (infection models using both sensitive and resistant species). Although the underlying mechanism has not been elucitated, the chemical structure responsible for this BRM activity has been recognized as the thio-thiazolyl moiety at C3 position of the cephem nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)
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Inserm U.294, CHU X. Bichat, Paris, France.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002439:Cefotaxime / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects; D007153:Immunologic Deficiency Syndromes / Q000188:drug therapy; D007155:Immunologic Factors / Q000627:therapeutic use; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007239:Infections / Q000188:drug therapy / Q000276:immunology; D010586:Phagocytes / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D002439:Cefotaxime; C033356:cefodizime
Valutazione sperimentale di antibiotici come immunomodulatori.