The main objective of this study is to demonstrate that the only administration of L-citrulline, can improve immune functions in critically ill patients at high risk of nosocomial infection.

This is a multicentric therapeutic trial, randomized and double blind: standard enteral nutrition plus L-citrulline (5 grams/12 Hours for 5 days from the admission in Intensive Care Unit (ICU)) versus standard enteral nutrition plus placebo.

Methods-Patients: Non-surgical patients admitted in medical intensive care unit, under mechanical ventilation for an expected duration > 2 days, without severe sepsis or septic shock, will be enrolled. Symptoms leading for ICU admission ongoing for five days maximum. On admission (before treatment), the severity will be evaluated with the Sepsis-related Organ Failure Assessment (SOFA) score together with an assessment of plasmatic arginine, cytokines (InterLeukin-6 (IL6) ), and expression of Human Leukocyte Antigen - antigen D Related (HLA-DR) by monocytes. The same evaluation will be repeated on day 3 (during treatment) and on day 7 (after treatment).

The enrolment of 100 patients is statistically enough to demonstrate a decreased SOFA scores in the L-citrulline group as compared to the placebo group on day 7.

Inclusion Criteria:

• age > 18 years
• medical patient (absence of recent surgery or trauma)
• initial aggression < 5 days
• mechanically ventilated with expected duration of mechanical ventilation > 2 days
• exclusive enteral nutrition
• absence of previous immunosuppression

Exclusion Criteria:

• severe sepsis
• septic shock
• obesity defined as BMI above 40
• pregnancy