Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be\r\nperformed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro.\r\nIn macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus) was paired once with\r\nstreptomycin (conditioned stimulus). Secretion of interleukin-6 (IL-6) was used as response measure. At evocation,\r\nconditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in\r\nthe learning phase (p�s < .05), regardless whether they received the conditioned stimulus or not at evocation.\r\nHowever, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p < .001). If\r\nfurther experiments confirm that simple learning can occur in immune cells, this may have bearings not only on\r\nimmune regulation, but also on the brain response to molecular signals detected in the periphery. Importantly,\r\nwhether capacities for simple learning in single cells extend beyond habituation, and how this would be\r\ndemonstrated, remain open questions.
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