Immunomodulating drugs increase resistance against sepsis in traumatized mice

John F. Hansbrough, Ramon Zapata Sirvent, Steven R. Shackford, David Hoyt, Walter H. Carter

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Immune suppression occurs frequently after major injury and undoubtedly contributes to infection and mortality in trauma patients. Prevention of such suppression may lead to decreased infection and improved survival in trauma patients surviving the immediate insult of injury. Suppressor-cell activation appears to play a key role in immune suppression after major injury. For several years we have studied the effects on immune functions after injury of various drugs which have been shown in the immunologic literature to have inhibitory effects on suppressor cell populations. H2 antagonists may inhibit suppressor cell activation by blocking surface H2-receptors, which are present in higher numbers on suppressor cells than on helper cells. Prostaglandin inhibitors may block the multiple immune suppressive effects of prostaglandins, particularly PGE2. Immunological studies suggest that low- dose cyclophosphamide selectively inhibits the proliferation of suppressor T cells. Our previous work suggested that such drugs preserve cell-mediated immune functions after injury. In experiments reported here, we utilized a standard hindlimb crush injury and amputation in mice, followed in 24 hrs by polymicrobial septic challenge using cecal ligation and 23-gauge needle puncture (CLP). Nontraumatized (control) mice had a 36.2% mortality after CLP; when crush injury/amputation was followed by CLP in 24 hrs the mortality rose to 63.8% (p < 0.0035). When mice were given 24 hrs before crush/amputation: cimetidine, an H2-antagonist (10 mg/kg/day); ibuprofen, a prostaglandin blocker (5 mg/kg/day); or cyclophosphamide (2.5 mg/kg/day), and a second dose on the day of trauma, with CLP 24 hrs later, subsequent mortality was not different from the mortality in nontraumatized, control mice (p < 0.0035). Specific immunomodulating therapy aimed at inhibiting suppressor cell activation or proliferation appears to improve resistance to lethal infection after trauma. The mechanisms of action of these drugs after injury deserve further study.

Original languageEnglish (US)
Pages (from-to)625-630
Number of pages6
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume26
Issue number7
StatePublished - Jan 1 1986
Externally publishedYes

Fingerprint

Drug Resistance
Sepsis
Wounds and Injuries
Amputation
Mortality
Cyclophosphamide
Prostaglandins
Infection
Pharmaceutical Preparations
Prostaglandin Antagonists
Histamine H2 Receptors
Ibuprofen
Cimetidine
Hindlimb
Helper-Inducer T-Lymphocytes
Punctures
Dinoprostone
Needles
Ligation
T-Lymphocytes

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Surgery

Cite this

Immunomodulating drugs increase resistance against sepsis in traumatized mice. / Hansbrough, John F.; Zapata Sirvent, Ramon; Shackford, Steven R.; Hoyt, David; Carter, Walter H.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 26, No. 7, 01.01.1986, p. 625-630.

Research output: Contribution to journalArticle

Hansbrough, John F. ; Zapata Sirvent, Ramon ; Shackford, Steven R. ; Hoyt, David ; Carter, Walter H. / Immunomodulating drugs increase resistance against sepsis in traumatized mice. In: Journal of Trauma - Injury, Infection and Critical Care. 1986 ; Vol. 26, No. 7. pp. 625-630.
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