title: Learning in a simple biological system: a pilot study of classical conditioning of human macrophages in vitro.
abstract: 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.
authors.affiliation: Karolinska Institutet, Osher Center for Integrative Medicine, Department of Clinical Neuroscience, Stockholm, Sweden.
authors.forename: Gustav
authors.initials: G
authors.lastname: Nilsonne
authors.forename: Alva
authors.initials: A
authors.lastname: Appelgren
authors.forename: John
authors.initials: J
authors.lastname: Axelsson
authors.forename: Mats
authors.initials: M
authors.lastname: Fredrikson
authors.forename: Mats
authors.initials: M
authors.lastname: Lekander
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D006185:Habituation, Psychophysiologic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D010865:Pilot Projects; D013307:Streptomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013307:Streptomycin
references.citation: Immunology. 1992 Feb;75(2):264-8
references.pmid: 1551689
references.citation: J R Soc Interface. 2009 May 6;6(34):463-9
references.pmid: 18835803
references.citation: Brain Behav Immun. 2010 Feb;24(2):176-85
references.pmid: 19698779
references.citation: Pharmacol Ther. 2007 Aug;115(2):208-22
references.pmid: 17597218
references.citation: PLoS Comput Biol. 2008 Nov;4(11):e1000235
references.pmid: 19043543
references.citation: Crit Care Med. 2008 Nov;36(11):3043-7
references.pmid: 18824917
references.citation: Nature. 2007 Jun 21;447(7147):916-7
references.pmid: 17581569
references.citation: Curr Biol. 2008 Jun 24;18(12):R527-30
references.pmid: 18579098
references.citation: Science. 1976 Dec 10;194(4270):1178-81
references.pmid: 186870
references.citation: Fed Proc. 1985 Jan;44(1 Pt 1):108-11
references.pmid: 2578415
references.citation: J Biosci. 2009 Oct;34(4):633-46
references.pmid: 19920348
references.citation: Ann N Y Acad Sci. 1985;443:8-21
references.pmid: 3860080
references.citation: Psychol Rep. 2006 Jun;98(3):705-11
references.pmid: 16933666
references.citation: Nature. 2007 Jun 21;447(7147):972-8
references.pmid: 17538624
references.citation: J Exp Med. 1995 May 1;181(5):1887-92
references.pmid: 7722463
references.citation: J Intern Med. 2005 Feb;257(2):126-38
references.pmid: 15656872
references.citation: Nature. 2009 Jan 29;457(7229):544-5
references.pmid: 19177118
references.citation: Nature. 2002 Dec 19-26;420(6917):853-9
references.pmid: 12490958
references.citation: Br J Pharmacol Chemother. 1960 Dec;15:506-9
references.pmid: 13790097
references.citation: Eur J Pharmacol. 1972 May;18(2):201-3
references.pmid: 4338756
references.citation: Science. 1983 Sep 16;221(4616):1201-3
references.pmid: 6612335
references.citation: Proc Natl Acad Sci U S A. 1979 Dec;76(12):6675-9
references.pmid: 293753
references.citation: Science. 2008 Jun 6;320(5881):1313-7
references.pmid: 18467556
references.citation: Phys Rev Lett. 2008 Jan 11;100(1):018101
references.pmid: 18232821
references.citation: Trends Immunol. 2009 Oct;30(10):475-87
references.pmid: 19781994
references.citation: Scand J Psychol. 1969;10(1):16-20
references.pmid: 5353393
references.citation: J Virol. 2001 Aug;75(16):7543-54
references.pmid: 11462026