Background:

- The drug rosuvastatin (also called Crestor) is used to lower cholesterol levels in people with elevated cholesterol levels. Recent studies have suggested that rosuvastatin may affect the immune system and reduce inflammation, but the reason for this effect is unclear. Researchers are interested in testing the effect of rosuvastatin on the immune systems of healthy volunteers with good cholesterol levels.

Objectives:

- To evaluate the effect of rosuvastatin on the immune systems of healthy volunteers.

Eligibility:

- Healthy individuals at least 18 years of age who have an acceptable blood level of LDL cholesterol (below 160).

Design:

• Participants will be screened with a medical history and physical examination, as well as blood tests to check general health, cholesterol levels, liver function, and the C-reactive protein (which responds to inflammation).
• Participants will not be permitted to take most prescription and over-the-counter medications that affect the immune system, including antihistamines and certain pain relievers. For 1 week before the study, participants will have a wash-out period without any of these medications.
• Participants will take rosuvastatin daily for 4 weeks, always in the evening (to ensure consistent blood sample results).
• Participants will provide blood samples at the following time points: (1) immediately before the start of the rosuvastatin treatment, (2) after 2 weeks of treatment, (3) after 4 weeks of treatment, and (4) 2 weeks after the end of treatment.

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.

• 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.