CYTOKINE RESPONSE ASSESSMENT
Background
The human immune system is profoundly complex and animal models are often incapable of demonstrating the in vivo human effects of a novel immune modulating therapy. A client developed a Complement inhibitor for treatment of autoimmune diseases. A phase I healthy volunteer study found that 2 subjects developed a tachycardia, leucocytosis and an elevated CRP (no cytokine measurements performed). The most likely cause of the response was an infection however the IRB wanted to confirm the safety of the molecule in terms of cytokine response.
Prototrial Strategy
Analytical Strategy
Whole blood samples were obtained from 3 male and 3 female healthy volunteers. The samples were assayed under the following conditions:
Outcomes
The LPS control produced a strong positive cytokine response (IFN-ɣ, IL-10, IL-13, IL-1β, and TNF-α). There was no significant difference between the negative control and drug treated samples, Subsequent clinical studies have not found any cytokine response to therapy.
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