Effects of Rosuvastatin on the Immune System in Healthy Volunteers With Normal Cholesterol

Statins are drugs that inhibit cholesterol synthesis and are used extensively for primary and secondary prevention of heart disease. Their benefit to patients with heart diseases appears to exceed that predicted from cholesterol lowering alone. A recent study has found benefits of statin therapy in patients with normal cholesterol and high C-reactive protein, a marker of inflammation, suggesting that statins exert an anti inflammatory effect in addition to the well known cholesterol lowering activity. Studies in mice have revealed mixed observations regarding the role of statins in inflammation. Therefore the Center for Human Immunology, Autoimmunity and Inflammation is conducting this trial to study the effects of statins on the immune system and the inflammatory response in healthy volunteers with normal cholesterol levels, and normal or elevated C-reactive protein levels.

The primary objective is to characterize the immune system before and during statin therapy.

Primary outcomes

• To elucidate the effects of a four week course of statins on the immune system in healthy volunteers with normal cholesterol with or without elevated C- reactive protein.: An understanding of the mechanism by which statins effect the immune system may help us better define the patient population that might benefit from such therapy and potentially develop drugs that act more selectively and potently on the relevant immunologic pathway(s). We will also address the potential antithrombotic activity of statins.This study has been slow to recruit healthy subjects with elevated CRP, often because subjects with elevated CRP had mild abnormalities on a detailed history and physical exam, such as impaired fasting glucose. In addition, preliminary analysis of the cohort of normal CRP suggests a significant reduction in serum IL-17 during statin therapy. Psoriasis is an inflammatory disease that affects the skin and the joints, is assumed to be IL-17 driven17, and subjects are usually free of systemic imunosuppression.

Secondary outcomes

• To describe the effects of statins on platelet activity and coagulation during thrombus formation.

Sex: All, ages: 18 Years to 99 Years, accepts healthy volunteers

* INCLUSION CRITERIA:
* Healthy volunteer (health status confirmed by brief History and Physical Exam and routine blood work as determined by the screening protocol)
* Age greater than or equal to18 years of age
* LDL < 160 mg/dL
* Ten subjects must have hsCRP < 2mg/L, and ten subjects must have hsCRP greater than or equal to 2 mg/L
* Subjects with psoriasis that are otherwise healthy, who have not received any systemic imunosuppression in the past 6 months
* Subjects with fasting glucose < 125 mg/dL

EXCLUSION CRITERIA:

* Female subjects may not be pregnant or lactating due to minor side effects of use of statins in a non-benefit study.
* Abnormal LFT s, i.e. AST > 34 U/L; ALT > 41 U/L; T. Bilirubin >1.0 mg/dL; Alkaline Phosphatasse > 116 U/L.
* Other contraindication to statins (i.e. inadequately treated hypothyroidism, renal impairment, liver disease, elevated transaminases, diabetes mellitus or hypersensitivity to a statin)
* Subjects unable to comprehend the investigational nature of the procedure or unable or unwilling to sign the consent.
* Statin usage within the last six months prior to enrollment.
* Diabetes mellitus
* Subjects not willing to participate in the gene expression analysis and whole genome expression and polymorphisms studies portion of this protocol.

• Results publication: Karmaus PW, Shi M, Perl S, Biancotto A, Candia J, Cheung F, Kotliarov Y, Young N, Fessler MB; CHI Consortium. Effects of rosuvastatin on the immune system in healthy volunteers with normal serum cholesterol. JCI Insight. 2019 Nov 1;4(21):e131530. doi: 10.1172/jci.insight.131530. PMID 31573980

• Angelique Biancotto, Ph.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)