Elevated temperature alters cytokine output and c-Jun N-terminal kinase signaling downstream of toll-like receptor activation
Fever is a fundamental and important response to infection. Previous studies have shown that alterations in temperature can alter the phenotype of innate immune cells, such as phagocytic ability, but the effects of elevated temperature on the molecular mechanisms that underlie these differences remain poorly understood. Here, we describe alterations in cytokine production following stimulation with lipopolysaccharide or polyinosinic:polycytidylic acid when U937 cells, a human monocyte cell line, are incubated at elevated temperature. The observed responses differ depending on the stimulus, suggesting that they are programmed responses to different stimuli rather than a non-specific response to temperature. We also show that signaling pathways may be ‘rewired’ during hyperthermia to signal through alternative pathways. These findings demonstrate the critical importance of considering temperature as a variable when studying immune responses and host-defense mechanisms in the context of infectious diseases that cause fever.