Interleukin-6 and the serotonergic system of the medulla oblongata in the sudden infant death syndrome.
Mild infection may trigger sudden death in the vulnerable infant by cytokine interactions with a compromised medullary serotonergic (5-HT) system, leading to disrupted cardiorespiratory regulation and sleep-related sudden death. The cytokine interleukin (IL)-6 is elevated in the cerebrospinal fluid in SIDS. We tested the hypothesis that the expression of IL-6 receptors (IL-6R) and/or gp130 (involved in IL-6R signaling) is altered in the medullary 5-HT system in SIDS. Immunohistochemistry of IL-6R and gp130 was performed on medullae from 25 SIDS infants, 20 infectious deaths, and 14 controls using a semi-quantitative grading system. In the SIDS cases, mean IL-6R intensity grade in the arcuate nucleus (major component of medullary 5-HT system) was significantly higher than in the control group (2.00 +/- 0.07 vs. 1.77 +/- 0.08, P = 0.04), with no other differences in IL-6R or gp130 expression at any other site. Arcuate 5-HT neurons expressed IL-6R, indicating a site of IL-6/5-HT interaction. In SIDS, IL-6R expression is abnormal in the arcuate nucleus, the putative human homolog of rodent ventral medullary chemosensitivity sites involving 5-HT. Aberrant interactions between IL-6 and the arcuate nucleus may contribute to impaired responses to hypercapnia generated by infection (hyper-metabolism) combined with rebreathing.
Rognum
Ingvar Jon
IJ
Department of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA. ingvarjo@stud.ntnu.no
Haynes
Robin L
RL
Vege
Ashild
A
Yang
May
M
Rognum
Torleiv O
TO
Kinney
Hannah C
HC
D000704:Analysis of Variance; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007239:Infections / Q000150:complications; D015850:Interleukin-6 / Q000134:cerebrospinal fluid / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D012307:Risk Factors; D012701:Serotonin / Q000378:metabolism*; D013398:Sudden Infant Death / Q000134:cerebrospinal fluid / Q000209:etiology*
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D012701:Serotonin