More recent evidence
It was Wagner von Jauregg in 1917 who gave an enormous impetus to the research with his work that fever was an effective treatment of neurosyphilis with malarial fever[37]. One of the most important outcomes of this research in recent years has been the discovery of a single mononuclear cell product, (IL-1, whose effects include induction of fever and activation of T-lymphocytes. Numerous substances from outside the body, exogenous pyrogens (ExPs), initiate the fever cycle. Endotoxin of Gram-negative bacteria is the most potent ExPs. The ExPs stimulate monocytes, fixed-tissue macrophages and reticuloendothelial cells to produce and release endogenous pyrogens, of which IL-1 is the most important. IL-1 acts on the hypothalamic thermoregulatory center through mediators, particularly PGE2, to raise the thermostatic set-point. The hypothalamic center accomplishes heat production by inducing shivering and heat conservation through vaso-constriction. At an established degree, fever is regulated by this centre (even at a temperature of over 41.0 °C) and heat production approximates loss, as in health, though at a higher level of the set-point. Therefore fever does not climb up relentlessly. IL-1 has other functions, including: Playing a primary role in the induction of inflammatory responses, such as neutrophil accumulation and adherence, and vascular changes. Stimulating the liver to synthesis certain proteins, acute-phase proteins, such as fibrinogen, haptoglobin, ceruloplasmin and CRP. T-cell and B-cell proliferation and activation, IL-1 activates T-lymphocytes to produce various factors, such as INF and IL-2, which are vital for immune response.
The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the role of fever.