Immunopharmacology of Antibiotics: Direct and Indirect Immunomodulation of Defence Mechanisms

Abstract

Antibiotics can alter the host's reaction to an infection (itself an immunomodulating event) in various ways. Indirect actions involve killing of bacteria, changing the intestinal flora, intrinsic antigenicity and preventing bacteria making virulence factors. Direct actions are upon phagocytic function, chemotaxis and lymphocyte activities. Immunomodulation can be positive ("pro-host") or negative, and can be quantitated by means of the parameter "immune index". Among the cephalosporins, cefodizime shows the greatest positive immunomodulating activity, due to the unique nature of the 3-sidechain. Cefotaxime has an immunodepressing effect in vitro. The oral cephalosporin cefaclor appears to have a beneficial effect on polymorph function. While immunomodulation by antibiotics may appear marked in in vitro and ex vivo experiments, and in animal models, this phenomenon does not appear to have decisive effects therapeutically.

Spontaneous Pain, Both Neuropathic and Inflammatory, Is Related to Frequency of Spontaneous Firing in Intact C-Fiber Nociceptors

“…would reduce inflammatory responses to bacterial infection (if present despite aseptic operating conditions), or may directly influence inflammatory responses (Hamilton-Miller, 2001) such as that to chromic gut.…”

Antibiotic resistance from two perspectives: man and microbe

“…Where antibiotics have to be used, 'use less, less better' should be the theme; possible interventions include refining of dosage regimens, targeting, improving compliance, restricting prophylaxis to where it is of proven value, continuing education of the profession and the public and reduction of excessive usage outside medical and veterinary practice. Less conventional approaches might involve application of better understanding of immunomodulating agents [6,7] and advances in chronobiology [8,9].…”

Clinical veterinarian’s perspective of non-human primate (NHP) use in drug safety studies

“…These antibiotics have been shown to have many immunomodulatory effects. Toxicities, such as suppression of antibody responses (i.e., doxycycline) (Woo et al, 1999), potentiating phagocytosis by WBC (i.e., certain cephalosporins, fluoroquinolones) (Gemmell, 1993;Hamilton-Miller, 2001), inhibition of transcription factors (i.e., telithromycin) (Leiva et al, 2008), reductions in tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-8 production (i.e., tetracycline, doxycycline, fluoroquinolones) (Woo et al, 1999;Kolios et al, 2006;Lahat et al, 2007), modulation of interferon (IFN)-γ levels (i.e., β-lactams) (Brooks et al, 2005), modulation of the glutamate transporter GLT1 (i.e., β-lactams) (Rothstein et al, 2005), reduction of T-cell activation by modulation of cellular antigen-presentation and impairment of antigen-specific T-cell migration into the CNS rather than a modulation of central glutamate homeostasis" (i.e., β-lactams) (Melzer et al, 2008), inhibition of matrix metalloproteases (i.e., doxycycline) (Errami et al, 2008), and inhibition of macrophage phagocytic activity (i.e., metronidazole) (Fararjeh et al, 2008) are examples of the published effects of some antibiotics (Van Vlem et al, 1996).…”