To create a fever, cytokines bind to receptors on hypothalamic endothelium. Increase levels of PGE2 increase in periphery accounts for nonspecific myalgias and arthralgias often accompanying fever. PGE2 binds to EP-3 (PGE2 receptor) on glial cells. Rapid release of __ from __ activates neuron terminals that extend into the thermoregulatory center. Some microbial toxins bind to TLR on hypothalamic endothelium to induce fever.