Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure

Kathryn Felmet, Mark W. Hall, Robert S B Clark, Ronald Jaffe, Joseph A. Carcillo

Research output: Contribution to journalArticle

183 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3765-3772
Number of pages8
JournalJournal of Immunology
Volume174
Issue number6
StatePublished - Mar 15 2005
Externally publishedYes

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Lymphopenia
Multiple Organ Failure
Sepsis
Lymphocyte Count
Apoptosis
Critical Illness
Prolactin
Pediatric Intensive Care Units
Thymus Gland
Observational Studies
Autopsy
Spleen
Lymph Nodes
Lymphocytes
Staining and Labeling

ASJC Scopus subject areas

  • Immunology

Cite this

Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure. / Felmet, Kathryn; Hall, Mark W.; Clark, Robert S B; Jaffe, Ronald; Carcillo, Joseph A.

In: Journal of Immunology, Vol. 174, No. 6, 15.03.2005, p. 3765-3772.

Research output: Contribution to journalArticle

Felmet, Kathryn ; Hall, Mark W. ; Clark, Robert S B ; Jaffe, Ronald ; Carcillo, Joseph A. / Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure. In: Journal of Immunology. 2005 ; Vol. 174, No. 6. pp. 3765-3772.
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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.",
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