Prolonged Lymphopenia, Lymphoid Depletion, and Hypoprolactinemia in Children with Nosocomial Sepsis and Multiple Organ Failure

Abstract

Lymphopenia and lymphoid depletion occur in adults dying of sepsis. Prolactin increases Bcl-2 expression, suppresses stress-induced lymphocyte apoptosis, and improves survival from experimental sepsis. We hypothesized that prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia occur in children dying with sepsis and multiple organ failure (MOF). Fifty-eight critically ill children with and 55 without MOF admitted to a university hospital pediatric intensive care unit were enrolled in a prospective, longitudinal, observational clinical study. Prolactin levels and absolute lymphocyte count were measured on days 1, 3, 7, 14, and 21. Lymph node, thymus, and spleen autopsy specimens were examined for lymphoid depletion, with immunohistochemical staining for CD4, CD20, and CD21 and for lymphoid apoptosis. Prolonged lymphopenia (absolute lymphocyte count < 1000 for >7 days) occurred only in children with MOF (29 vs 0%, p < 0.05) and was associated independently with nosocomial infection (odds ratio (OR), 5.5, 95% confidence interval (CI), 1.7–17, p < 0.05), death (OR, 6.8, 95% CI, 1.3–34, p < 0.05), and splenic and lymph node hypocellularity (OR, 42, 95% CI, 3.7–473, p < 0.05). Lymphocyte apoptosis and ante/postmortem infection were observed only in children with lymphoid depletion. Prolonged hypoprolactinemia (>7 days) was more common in children with MOF (17 vs 2%, p < 0.05) and was associated independently with prolonged lymphopenia (OR, 8.3, 95% CI, 2.1–33, p < 0.05) and lymphoid depletion (OR, 12.2, 95% CI, 2.2–65, p < 0.05). Prolonged lymphopenia and apoptosis-associated depletion of lymphoid organs play a role in nosocomial sepsis-related death in critically ill children. Prolonged hypoprolactinemia is a previously unrecognized risk factor for this syndrome.

Immunoparalysis and Adverse Outcomes from Critical Illness

“…Monneret and others have recently demonstrated associations between immunoparalysis and the subsequent development of a T reg -dominant adaptive immune response [55,56]. It has also been clearly shown in critically ill adults [57] and children [58] that lymphocyte apoptosis and lymphopenia are common in ICU nonsurvivors. The temporal and causal relationships between innate and adaptive immune dysfunction in critical illness remain incompletely understood.…”

Nosocomial infections in brazilian pediatric patients: using a decision tree to identify high mortality groups

“…Even if it were, its calculation only at admission, as in many hospitals, would not reflect the severity of illness at the time of the NI; this would be another limitation, and its calculation twice was not feasible (no grant support). Various previous studies [9,10,15] reported intrinsic and extrinsic risk factors, according to where the research took place (different patient populations and medical practices); so, it is always important to know the institutional environment. Although our data were collected some time ago, our findings are similar to what has been reported recently; infection control teams must focus on the reduction/ appropriateness of invasive devices and decrease inadequate antimicrobial treatment of infection, since they cannot change the patient's clinical status or underlying diseases.…”

“…Nevertheless, few studies have analyzed mortality data [9,10], and this has not been done in Brazilian public pediatric hospitals. This is needed in order to make evaluate infection control programs.…”

L’interleukine-7 comme thérapeutique immuno-adjuvante dans le traitement du choc septique

“…Toutes les populations lymphocytaires sont affectées, à l'exception des lymphocytes T régu-lateurs (voir plus loin) [8]. L'amplitude de la lymphopénie est corrélée à la survenue d'infections nosocomiales et/ou à la mortalité [9][10][11]. Elle peut durer plusieurs semaines, et l'absence de retour à un compte lymphocytaire normal est associée à des complications infectieuses tardives.…”