Microbial and Host Metabolites at the Backstage of Fever: Current Knowledge about the Co-Ordinate Action of Receptors and Molecules Underlying Pathophysiology and Clinical Implications

Abstract

Fever represents an elevation of body temperature, that exerts a protective effect against pathogens. Innate immune cells and neurons are implicated in the regulation of body temperature. Pathogen-associated molecular patterns, i.e., lipopolysaccharides from Gram-negative bacteria and peptidoglycan and lipoteichoic acid from Gram-positive bacteria are exogenous pyrogens, that bind to Toll-like receptors on immune and non-immune cells. The subsequent release of pro-inflammatory cytokines [interleukin-1 (IL-1), IL-6 and Tumor necrosis factor-alpha] and their passage through the brain trigger the febrile response. In fact, neurons of the pre-optic area produce prostaglandin E2 (PGE2), that, in turn, bind to the PGE2 receptors; thus, generating fever. Apart from classical non-steroidal anti-inflammatory drugs, i.e., aspirin and acetaminophen, various botanicals are currently used as antipyretic agents and, therefore, their mechanisms of action will be elucidated.

Current Views about the Inflammatory Damage Triggered by Bacterial Superantigens and Experimental Attempts to Neutralize Superantigen-Mediated Toxic Effects with Natural and Biological Products

“…Among them, IL-1 and TNF-alpha contribute to extending the inflammatory status, increasing vascular permeability and, ultimately, provoking multiorgan failure and shock [ 57 ]. Furthermore, the chemokines, IL-8, monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, are induced via SEA, SEB and TSST-1 [ 58 , 59 ]. Systemic and intranasal exposure to SEB has been shown to induce infiltration of neutrophils and mononuclear cells into tissue with increased vascular permeability and acute lung injury (ALI) [ 60 , 61 ].…”

Crosstalk between the Resident Microbiota and the Immune Cells Regulates Female Genital Tract Health

“…in the vagina cause an increase in SCFAs, especially acetate, as well as the triggering of the anti-inflammatory pathway sustained by Treg cells [87][88][89]. Conversely, in AV, other uropathogens are able to increase the expression of an array of pro-inflammatory cytokines, even including IL-1 beta, IL-6, IL-8, and TNF-alpha, as an indication of the local immune imbalance between inflammatory and anti-inflammatory forces [90,91]. Quite interestingly, some bacteria, in the course of AV, become resistant to the host immune response, as in the case of S. aureus, which evade the microbicidal activity locally produced by nitric oxide (NO) [92,93].…”

Gut Microbiota and Immune System in Necrotizing Enterocolitis and Related Sepsis

“…Symptoms in some children do not manifest themselves clinically, and they may develop a septic condition without the disease being diagnosed. The condition can rapidly progress from mild to severe within 72 h. Laboratory hematological test results are usually neutropenia, thrombocytopenia, unbalanced hemostasis (prolongation of partial thromboplastin time), metabolic acidosis, anemia, and altered sepsis biomarkers [18][19][20][21]. Non-severe cases of NEC can be effectively treated with intestinal food retention, stomach decompression with a nasogastric tract, and the initiation of broad-spectrum antibiotics.…”