Sick and tired of being sick and tired

Citation: Vulliemoz NR, Xiao E, Xia-Zhang L, Ferin M, Wardlaw SL. Melanocortin modulation of inflammatory cytokine and neuroendocrine responses to endotoxin in the monkey. Endocrinology. 2006 Jan 12; [Epub ahead of print]

Summary of Experiment: Primates were sedated and placed in primate chair overnight. Blood was drawn at 8 am and then saline or one of three experimental agents was injected. At 10 am, animals were injected with enough E. coli to induce a significant immune response and “sickness behaviors.” Blood was taken every 30-60 minutes for the next 7 hours. This experiment was performed 3 times with 3 weeks recovery between sessions. Immune and stress responses were measured. Baselines were taken by performing the procedure without the E. coli injection (x3). Immune and stress responses were measured. Short term reaction was studied by putting primates in chairs the morning of the experiment (0800), given saline or experimental agent for a longer period (until 1300), then given E. coli and monitored until 1800. This experiment was performed 3 times with 3 weeks recovery between sessions.

Some of the agents affected aspects of the immune response that increase and decrease inflammation. The way the stress system (The “HPA axis”) responds to these inflammation messengers was also affected.

My Notes:

• There is no mention of managing the “sickness behaviors” in these monkeys. E. coli can be horrid. Symptoms include intense abdominal pain, bloody diarrhea, fever, loss of appetite, vomiting and dehydration.
• In the discussion, they address the fact that animals used in both parts of the experiment responded differently to phase two than “fresh” animals. The drugs tested could have long-term effects on the immune or hormone systems, or interact with one another when one agent is administered after the other.
• Authors mention that their results mirror rodent studies – Wardlaw also does rodent experiments. It's not clear why they are repeating work in primates.

Author Affiliation: Departments of Medicine and Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY 10032

Funding Acknowledged: NIH Grant MH55708 (Looks like ~ $1.7Mover five years)