What are pyrogens?
One of the ways to combat disease is fever, it is considered an adaptive mechanism against infections. During a microbial infection, phagocytic leukocytes derived from the bone marrow are stimulated. Thus, they release a hormone that was referred to endogenous pyrogen long ago, and corrected later in 2004 to “pyrogenic cytokines” that causes fever. In fact, cytokines are proteins concerned with cell signalling, they function in mediating fever where their domain of action exists within damaged tissues, brain and circulating factors. The destination of pyrogens is the preoptic area of the anterior hypothalamus where the thermoregulatory center resides, it's center leads to increasing the normal body temperature “set-point”.
AUTO-PHASE RESPONSE “pyrogenic reaction”
Pyrogens initiate a response called auto-phase response following the production of acute phase proteins by the liver.
The response as a step-wise list:
-C-reactive protein (CRP) level increase due to infection, CRP then binds to phosphoryl choline present on the surface of bacteria.
-Mannose-binding protein binds mannose on bacteria surface.
-Also, both CRP and mannose-binding protein act as opsonins and mimic the function of antibodies to facilitate phagocytosis.
-IL-1, IL-6, and TNF-alpha cause an increase in circulating neutrophils. Besides, they induce the migration of dendritic cells to lymph nodes becoming antigen presenting cells “APCs” which is part of the adaptive response.
-Furthermore, IL-1 and TNF-alpha make endothelial upgrade expression of their adhesion molecules
-IFN-alpha and IFN-beta interfere with viral replication, increase MHC class I for uninfected cells to resist natural killer cells “NK cells”, so that infected cells become more susceptible to death by CD8+ (cytotoxic) T cells.
-Finally, TGE-beta cytokine terminates the inflammatory response.
References:
-Luheshi G, Rothwell N. Cytokines and fever. Int Arch Allergy Immunol. 1996 Apr;109(4):301-7. doi: 10.1159/000237256. PMID: 8634513.
-Bernheim HA, Block LH, Atkins E. Fever: pathogenesis, pathophysiology, and purpose. Ann Intern Med. 1979 Aug;91(2):261-70. doi: 10.7326/0003-4819-91-2-261. PMID: 223485.