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Patients with impaired immune function, as determined by their lack of reaction to certain skin tests, are said to have walk-in anergy (WA). Increased postoperative mortality has been noted in patients with WA; in most of these cases, the patients had developed sepsis (widespread response to severe infection). To learn more about the failure of WA patients' immune systems, the function of polymorphonuclear leukocyte neutrophils (PMNs) was studied. PMNs are a type of white blood cell that is activated as part of the nonspecific immune response (which is exclusive of the antibody-generating system). When infection occurs, PMNs are recruited to the infected region. The rate of PMN recruitment in WA patients was of particular interest, and was evaluated in 9 patients with WA, and in 5 patients and 5 healthy individuals, who were identified as walk-in reactive (WR). WA or WR status was determined by the magnitude of the response to skin tests using five antigens (proteins that commonly elicit an immune response). In addition, the number of PMNs delivered to a small area of the forearm was measured (using the skin window technique), as was the chemoattractant ability of the fluid in which the PMNs were recovered. This was of interest because PMNs 'home' to an infected region as a result of chemoattraction. The results revealed that WA patients had higher rates of PMN delivery than WR patients, who, in fact, had the same rate as WR controls. Fluid from WA patients also showed a greater chemoattractant ability than that of WRs. In addition, lactoferrin levels (a measure of white blood cell density) were higher in WAs than WRs or controls. The data suggest that patients with WA have a 'stimulated' immune system; the implications of this finding for postoperative recovery remain to be determined. (Consumer Summary produced by Reliance Medical Information, Inc.)

OBJECTIVE: To determine whether the inflammatory microenvironment primes neutrophils for increased microbicidal activity. DESIGN: In vitro studies of host defense were performed on surgical patients. SETTING: A tertiary care, university hospital. PATIENTS: A volunteer sample of hospitalized preoperative, noninfected surgical patients. INTERVENTION: Exudative neutrophils were collected from skin-blister chambers and functionally compared with circulating neutrophils. METHODS: Flow cytometry was used to evaluate directly neutrophil microbicidal activity (using fluoresceinated Candida albicans), formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide production (using 123 dihydrorhodamine), and surface expression of CDllb, CD16, and the fMLP receptor. In vitro tumor necrosis factor α was used to determine the possibility and extent of further priming in both circulating and exudative neutrophils. RESULTS: Exudative polymorphonuclear neutrophils have enhanced microbicidal activity, superoxide production, and expression of CDllb, CD16, and the fMLP receptor. Exogenous tumor necrosis factor was able to prime circulating neutrophils but did not further augment superoxide production in exudative neutrophils. CONCLUSION: The microbicidal activity of neutrophils is enhanced after exudation and is associated with neutrophil priming. The inability of exogenous tumor necrosis factor to further augment superoxide production after exudation suggests that this priming has been maximized.(Arch Surg. 1994;129:99-105)

• We tested the hypothesis that anergy is associated with reduced delivery of mononuclear cells (MNCs) to delayed-type hypersensitivity sites and that cytokine (CK)-rich supernatants from mixed lymphocyte cultures overcome the defect. Significantly fewer MNCs were delivered to skin window chambers placed over purified protein derivative (PPD) injection sites of previously sensitized anergic patients compared with hospitalized PPD-reactive patients; coinjection of CK with PPD restored the MNC delivery in anergic patients to normal levels. The T cells cloned from a PPD+CK site of an anergic patient consisted of CD4+ and CD8+ cells whose capacities included cytotoxicity and lymphokine production. The frequency of PPD-reactive cells was 15 times greater than in the blood. Thus, the restoration by CK of the delivery of antigen-specific cells capable of participating in cell-mediated immunity in anergic patients may be feasible.(Arch Surg 1988;123:1470-1473)

• Because the majority of patients receiving intensive care are anergic to ubiquitous skin test antigens, prediction of clinical outcome cannot be based on their delayed-type hypersensitivity score, which is 0, but which is also a strong indicator of sepsis-related mortality in the preoperative patient. However, a cytokine-rich supernatant generated in the mixed lymphocyte culture reaction is able to induce an early skin reaction that peaks at 12 hours and wanes by 24 hours in some, but not all, anergic patients. Assessment of the clinical course of these patients demonstrated that only three of 25 patients who had a skin reaction larger than 5 mm died, compared with ten of 16 patients who failed to display this early reaction. Further analysis showed that both the cytokine-induced reaction and the acute physiology score significantly and independently contributed to the probability of death in anergic patients. These data suggest that the ability to generate a local inflammatory response to cytokines in anergic patients identifies a subpopulation of patients who have maintained some host-defense responsiveness and this response can be utilized to predict outcome.(Arch Surg 1988;123:1474-1476)