Inflammatory vulnerability associated with the rh5‐HTTLPR genotype in juvenile rhesus monkeys

• Published in: Genes, brain and behavior Vol. 12; no. 3; pp. 353 - 360
• Main Authors: Amaral, W. Z., Lubach, G. R., Bennett, A. J., Coe, C. L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2013; Blackwell; John Wiley & Sons, Inc
• Subjects: 5‐HTTLPR; allele polymorphism; Alleles; Animals; Arousal; Behavioral psychophysiology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Genes; Genotype; Genotype & phenotype; Heterozygote; Homozygote; inflammation; Interleukin-6 - blood; Interleukin-6 - immunology; interleukin‐6; Leukocytes - immunology; lipopolysaccharide; Lipopolysaccharides - immunology; Macaca mulatta; Male; monkey; Neurotransmission and behavior; Polymorphism, Genetic - immunology; Primates; Promoter Regions, Genetic; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; serotonin; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin Plasma Membrane Transport Proteins - immunology; stress; Stress, Psychological - genetics; Stress, Psychological - immunology; Monkey; Macaca mulatta; Genetic determinism; interleukin-6; Interleukin 6; Gene; Primates; Simioidea; Lipopolysaccharide; Genetics; Serotonin; 5-HTTLPR; Cytokine; Genotype; Inflammation; Vulnerability; Experimental study; Stress; Vertebrata; Allele; Mammalia; Serotonin transporter; Animal; Neurotransmitter; allele polymorphism; Polymorphism
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/gbb.12023

Individual variation in serotonergic function is associated with reactivity, risk for affective disorders, as well as an altered response to disease. Our study used a nonhuman primate model to further investigate whether a functional polymorphism in the promoter region for the serotonin transporter gene helps to explain differences in proinflammatory responses. Homology between the human and rhesus monkey polymorphisms provided the opportunity to determine how this genetic variation influences the relationship between a psychosocial stressor and immune responsiveness. Leukocyte numbers in blood and interleukin‐6 (IL‐6) responses are sensitive to stressful challenges and are indicative of immune status. The neutrophil‐to‐lymphocyte ratio and cellular IL‐6 responses to in vitro lipopolysaccharide stimulation were assessed in 27 juvenile male rhesus monkeys while housed in stable social groups (NLL = 16, NS = 11) and also in 18 animals after relocation to novel housing (NLL = 13, NS = 5). Short allele monkeys had significantly higher neutrophil‐to‐lymphocyte ratios than homozygous Long allele carriers at baseline [t(25) = 2.18, P = 0.02], indicative of an aroused state even in the absence of disturbance. In addition, following the housing manipulation, IL‐6 responses were more inhibited in short allele carriers (F1,16 = 8.59, P = 0.01). The findings confirm that the serotonin transporter gene‐linked polymorphism is a distinctive marker of reactivity and inflammatory bias, perhaps in a more consistent manner in monkeys than found in many human studies. Carriers of the short rh5‐HTTLPR allele evidenced a higher neutrophil‐to‐lymphocyte ratio in blood than their LL counterparts while in undisturbed housing conditions, indicative of an aroused state even in the absence of disturbance. In addition, S carriers underwent greater inhibition of cellular IL‐6 responses to LPS stimulation after rehousing with an unfamiliar monkey. The inhibitory effect of stress remained evident in S‐carriers even after adjusting for the number of mononucleocytes in circulation.