Food protein-induced enterocolitis syndrome (FPIES) is thought to be a non-IgE mediated food allergy syndrome. Affected infants typically demonstrate gastrointestinal symptoms after hours after ingestion of the offending food. Traditional allergy testing is not useful for this disorder because tests for food specific IgE are routinely negative. A diagnostic oral food challenge (OFC) is the only method to confirm the diagnosis of FPIES. This prospective study was undertaken to determine whether the atopy patch test (APT) is able to predict the results of the OFC. Nineteen infants with suspected FPIES by clinical history underwent APT to the suspected foods. After APT was performed, subjects underwent OFC to determine whether FPIES was present. The results of APT and OFC were compared and used to calculate sensitivity and specificity of the APT. APT predicted the results of oral food challenges in 28/33 instances. There were 16 cases of FPIES confirmed by oral food challenges. In all 16 cases of FPIES, the APT was positive to the suspected food. However, the APT was positive in five instances where the oral food challenge was negative. All 12 patients with a negative APT had a negative oral food challenge to the suspected food. APT appears to be a promising diagnostic tool for the diagnosis of FPIES.

Human alveolar macrophages obtained by bronchoalveolar lavage were labeled overnight with [3H]arachidonic acid. The cells were stimulated with calcium ionophore A23187, and the 20:4 oxygenated metabolites released into the culture medium were identified by reverse-phase HPLC. Leukotriene B4 was the major 20:4 metabolite produced by these cultures. Leukotriene B4 was identified by its reverse-phase HPLC elution time, its UV spectrum, and its chemotactic and chemokinetic activities for neutrophils. In addition, the macrophage. and neutrophil-derived leukotriene B4 free acids and methyl esters were found to have identical HPLC retention times.The leukotrienes are a recently discovered class of biologically active compounds that are formed from arachidonic acid (20:4) via the lipoxygenase pathway. They include leukotriene B4 [LTB4, (5S, 12R) dihydroxy-6, 14-cis-8, 10-trans-icosatetraenoic acid] (1), a compound with multiple proinflammatory actions, including chemotactic activity for neutrophils (2), and the slowreacting substances, leukotrienes C4 [(5S)-hydroxy-(6R)-S-glutathionyl-7,9-trans-11, 14-cis-icosatetraenoic acid] and D4 [(5S)-hydroxy-(6R)-S-cysteinylglycine -7,9-trans-11, 14 -cis-icosatetraenoic acid] (3, 4), which have vasoactive properties in addition to their contractile activity on select smooth muscle.All major classes ofgranulocytes have been shown to produce leukotrienes in vitro. However, recent studies with murine pulmonary and peritoneal macrophages indicated that macrophages may be a particularly rich source of these compounds, with LTC4 being the major lipoxygenase product (5, 6). To date, the macrophage is the only cell type known to synthesize substantial quantities of leukotrienes in response to inflammatory stimuli such as zymosan (5), and IgG (7) and IgE (8) immune complexes.In this paper, we report the capacity of human alveolar macrophages to produce leukotrienes. Pulmonary alveolar macrophages represent a large population of resident leukocytes in the lung and as such are believed to be the first line of defense against inhaled material. These cells therefore are ideally positioned to initiate inflammatory and allergic reactions in the lung. The available evidence suggests that human alveolar macrophages generate a low molecular weight chemotactic factor for neutrophils that may be a lipid (9). Our work identifies one such molecule and demonstrates that LTB4 is the major lipoxygenase product of these cells when they are stimulated with calcium ionophore A23187. MATERIALS AND METHODSIsolation of Human Alveolar Macrophages. Human alveolar macrophages were obtained by fiberoptic bronchoscopy with bronchoalveolar lavage in patients who had given informed consent. Lidocaine (2%) was used to anesthetize the nose and upper airways. The bronchoscope (model FB-19D, Pentex Precision Instrument, Norwood, NJ) was then passed transnasally and wedged into a subsegmental bronchus of the right middle lobe or lingula. Lidocaine (1%) was used as needed to suppress cough. Sterile saline, 100 to 1...

Murine macrophages synthesize specific cyclo-oxygenase and lipoxygenase metabolites of arachidonic acid (20:4) 1 after stimulation with zymosan (1-3) or particles coated with immune complexes of immunoglobulin G or E (4, 5). In man, less is known about the spectrum of oxygenated 20:4 compounds produced by mononuclear phagocytes. A number of studies have examined the cyclooxygeanse products of the human monocyte (6-1 1), the blood-borne precursor of the tissue macrophage. In addition, the synthesis of the lipoxygenase metabolite leukotriene B4 by the human alveolar macrophage has been reported (12).A particular problem in the study of 20:4 metabolism by the human monocyte has been platelet contamination. We now report a means of removing platelets adherent to the surfaces of freshly isolated monocytes. As a result, quantitative and qualitative comparisons of the biosynthetic pathways of platelets and monocytes were possible. Thromboxane was the predominant metabolite of monocytes incubated with particulate stimuli whereas exposure to the calcium ionophore A23187 yielded chiefly lipoxygenase products.

Levels of zymosan-induced arachidonic acid (20:4) metabolism by peritoneal macrophages elicited with inflammatory agents and resident macrophages were similar. Thyioglycollate (THIO)-elicited macrophages represented the exception; however, the diminished metabolism by these cells was reproduced by exposing resident cells to 5 mg/ml THIO broth in vitro. In contrast, reduced prostaglandin synthesis by macrophages from mice variously treated with the immunologic agents, Corynebacterium parvum or Bacille Calmette Guérin (BCG), closely correlated with enhanced antitoxoplasma activity, one measure of macrophage activation. This relationship, although not causative, suggested that the capacity for 20:4 metabolism is a function of the macrophage activation state. Modulation of macrophage 20:4 metabolism in vivo apparently required factors in addition to lymphocyte-derived products. Treatment of resident macrophages in vitro with BCG lymphokine was without effect on 20:4 release or prostaglandin synthesis. Activated macrophages from animals inoculated i.p. with C. parvum exhibited reduced 20:4 release and also failed to metabolize 70% of the 20:4 released in response to a zymosan stimulus. Consequently, the quantities of 20:4 metabolites formed were significantly less than expected from 20:4 release. These activated macrophages displayed greatly reduced synthesis of prostacylcin and leukotriene C compared with other 20:4 metabolites. It appeared that factors that regulate macrophage 20:4 metabolism influence the level of the inducible phospholipase and synthetic enzymes for specific 20:4 oxygenated products.