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Learning in a simple biological system: a pilot study of classical conditioning of human macrophages in vitro

Gustav Nilsonne123, Alva Appelgren1, John Axelsson1, Mats Fredrikson4 and Mats Lekander13*

Author Affiliations

1 Karolinska Institutet, Osher Center for Integrative Medicine, Department of Clinical Neuroscience, Stockholm, Sweden

2 Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology, Stockholm, Sweden

3 Stockholm University, Stress Research Institute, Stockholm, Sweden

4 Uppsala University, Department of Psychology, Uppsala, Sweden

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Behavioral and Brain Functions 2011, 7:47  doi:10.1186/1744-9081-7-47

Published: 18 November 2011


Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be performed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro. In macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus) was paired once with streptomycin (conditioned stimulus). Secretion of interleukin-6 (IL-6) was used as response measure. At evocation, conditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in the learning phase (p's < .05), regardless whether they received the conditioned stimulus or not at evocation.

However, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p < .001). If further experiments confirm that simple learning can occur in immune cells, this may have bearings not only on immune regulation, but also on the brain response to molecular signals detected in the periphery. Importantly, whether capacities for simple learning in single cells extend beyond habituation, and how this would be demonstrated, remain open questions.

associative learning; conditioning; habituation; in vitro; monocyte; macrophage; lipopolysaccharide; streptomycin; interleukin-6