Question

"Is there a benefit of inflammatory signaling inducing fever, loss of appetite and sleepiness? If so, what are those benefits? If not, then why would these occur?"

Answer 1

There is substantial evidence suggesting that a 1-4 degree rise in body temperature, which happens in fever, helps in resolution of infections and is associated with a better survival rate. Specific benefits:

• The direct effect of increased body temperature on the infectious potential of the pathogen. References in support:

Pockley AG, Calderwood SK, Santoro MG. Prokaryotic and eukaryotic heat shock proteins in infectious disease. Dordrecht: Springer; 2010.

Lwoff A. From protozoa to bacteria and virusesFifty years with microbes (Andre Lwoff) Annu Rev Microbiol. 1971;25:1–26.

Osawa E, Muschel LH. Studies Relating to the Serum Resistance of Certain Gram-Negative Bacteria. J Exp Med. 1964;119:41–51

• Promotes both innate and adaptive immunity by stimulating almost every step in the process. References in support:

Soehnlein O, Lindbom L. Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol. 2010;10:427–439

Loss of appetite and increased sleepiness or tiredness are symptoms developed due to the action of pro-inflammatory factors on the nervous system, and there is no evidence suggesting any real benefit to the host.

Mechanism of loss of appetite in inflammation- The action of pro-inflammatory cytokines and prostaglandin E2 on peripheral sensory neurons[neural pathway] and blood-brain barrier[humoral pathway] modulates the activity of feeding-related sites in hypothalamus and brainstem.

Increased sleepiness or fatigue has a multifactorial mechanism: increased levels of pro-inflammatory cytokines (interleukin-1 and −6 and tumor necrosis factor alpha), dysregulation of the hypothalamic-pituitary-adrenal axis, pain and behavioral symptoms. Reference for in-depth analysis of the multidimensional causation of fatigue - Hewlett S, Chalder T, Choy E, Cramp F, Davis B, Dures E, et al. Fatigue in rheumatoid arthritis: time for a conceptual model. Rheumatology (Oxford) 2011;50:1004–6. doi: 10.1093/rheumatology/keq282.