Increased plasma IgE levels in patients with sepsis after traumatic injury
Authors: Joseph T. DiPiro, Thomas R. Howdieshell, Robert G. Hamilton, N.Franklin Adkinson, Arlie R. Mansberger
Journal: Journal of Allergy and Clinical Immunology (1996)

We previously reported a retrospective study of 32 trauma patients, demonstrating that total plasma IgE was significantly increased after traumarelated sepsis syndrome when compared with IgE levels at the time of admission.1DiPiro JT Hamilton RG Howdieshell TR Adkinson NF Mansberger AR. Total IgE in plasma is elevated after traumatic injury and is associated with sepsis syndrome.Ann Surg. 1992; 215: 460-466Crossref PubMed Scopus (22) Google Scholar To investigate the temporal relationship of plasma IgE levels with traumatic injury and sepsis, we have conducted a prospective evaluation of 100 patients admitted to the Trauma Intensive Care Unit at the Medical College of Georgia, excluding patients with only head or burn injuries. Immunoglobulin (IgG, IgM, IgA, and IgE) and cytokine determinations were performed on plasma collected at the time of admission to the emergency department and three times weekly in the intensive care unit. In this report we describe temporal changes in three of these trauma patients who experienced substantial increases in plasma IgE (with eosinophilia) without evidence of allergic reactions or polyclonal B-cell hyperactivity. A 36-year-old man with no history of allergy experienced massive soft tissue avulsion, open pelvic fracture with expanding extraperitoneal hematoma, and a comminuted open femur fracture after a motor vehicle accident (Injury Severity Score = 34). During a 49-day stay in the intensive care unit, the patient had multiple organ failure (renal and hepatic) and septic shock associated with Pseudomonas pneumonia. He survived and was discharged from the hospital after 63 days. A 24-year-old man with no history of allergy sustained an impailment injury of the perineum after a fall, which resulted in vascular compromise of his extremity requiring eventual hip disarticulation (Injury Severity Score = 13). During a 31-day stay in the intensive care unit, the patient had Pseudomonas pneumonia, osteomyelitis, myoglobinuria, and sepsis. He also had oliguric renal failure requiring hemodialysis. He was eventually discharged from the hospital 62 days after admission with normal renal function. A 28-year-old woman with a history of allergy to pineapple only (as a child) experienced a lacerated kidney, pelvic fracture, 3% total body surface area burns, and closed head injury after a motor vehicle accident (Injury Severity Score = 30). During a 26-day stay in the intensive care unit the patient had streptococcal pneumonia, sepsis, and respiratory distress syndrome before being discharged from the hospital 33 days after admission. IgE, as measured by the enzyme immunoassay (ImX; Abbott, Abbott Park, Ill.) and absolute eosinophil counts are shown in Fig. 1. All patients were admitted with a plasma IgE concentration within the 95th percentile of the nonatopic distribution (300 ng/ml or less), which increased from 10- to 300-fold after the onset of sepsis. None of these patients experienced an identifiable allergic event. IL-4, as measured by ELISA, was undetectable in the plasma in patients 1 and 3 and was detected at a low concentration (<50 pg/ml) in patient 2. In contrast, some other trauma patients in this study had much higher IL-4 levels. A multiaeroallergen RAST evaluation of admission plasma samples (Phadiatop; Pharmacia, Uppsala, Sweden) was performed for each patient, and all results were determined to be negative (<100% of reference, indicating no specific IgE antibody to 15 of the most common aeroallergens). Total plasma IgG, IgM, and IgA were measured (by radial immunodiffusion) for admission plasma samples and samples obtained at the time of highest observed IgE level. For patients 1 and 2, IgG, IgM, and IgA plasma concentrations were all within the 95% confidence interval for the normal range. For patient 3, the IgM and IgA plasma concentrations were both 1.3 times the upper limit of the normal range. These results indicate that polyclonal B-cell activation is an unlikely explanation for the increased IgE levels. In previous studies1DiPiro JT Hamilton RG Howdieshell TR Adkinson NF Mansberger AR. Total IgE in plasma is elevated after traumatic injury and is associated with sepsis syndrome.Ann Surg. 1992; 215: 460-466Crossref PubMed Scopus (22) Google Scholar we determined that IgE was not appreciably elevated after elective surgical trauma. Also, in this study many patients with less severe injuries and no sepsis did not have elevation of IgE after injury. Patients experienced both a relative and absolute eosinophilia. Although total white blood cell counts were greatly elevated (up to 30,000/mm3 at some time for each patient), the percent eosinophils reached 30%, 11%, and 6% of total white blood cells (for patients 1, 2, and 3, respectively). These patients demonstrate that substantial but transient increases in plasma IgE concentrations may occur in association with sepsis after traumatic injury. The time courses of the IgE elevations suggest that they are related to an infection rather than to the traumatic events. The finding of elevated plasma IgE and eosinophil counts raises a number of questions as to whether IgE and eosinophils play a role in sepsis or are simply a consequence of cytokine changes that accompany sepsis. IL-4, which upregulates IgE production,2Sutton BJ Gould HJ. The human IgE network.Nature. 1993; 366: 421-428Crossref PubMed Scopus (479) Google Scholar is also a major regulatory factor for IL-1 and IL-1 receptor antagonist,3Fenton MJ Buras JA Donnelly RP. IL-4 reciprocally regulates IL-1 and IL-1 receptor antagonist expression in human monocytes.J Immunol. 1992; 149: 1283-1288PubMed Google Scholar both of which are believed to be important in the response to sepsis. For the patients in this report, we did not observe elevated IL-4 plasma concentrations (IL-5 and IL-13 were not measured). Cell-mediated immunity and interferon-γ production are reported to be decreased after traumatic injury,4Livingston DH Appel SH Wellhausen SR et al.Depressed interferon gamma production and monocyte HLA-DR expression after severe injury.Arch Surg. 1988; 123: 1309-1312Crossref PubMed Scopus (171) Google Scholar, 5Faist E Kupper TS Baker CC et al.Depression of cellular immunity after major trauma.Arch Surg. 1986; 121: 1000-1005Crossref PubMed Scopus (229) Google Scholar findings consistent with increased IgE production. Perhaps the relative balance of cytokines that regulate IgE production is altered after sepsis, favoring IgE production and eosinophilia. From a diagnostic viewpoint, these observations raise concerns about the collection of blood specimens for allergy evaluation (specifically, total plasma IgE measurement) while an individual is experiencing bacterial sepsis. Our study clearly shows that transient elevations of total plasma IgE occur in traumatically injured patients with sepsis.