Pollen Proteases Play Multiple Roles in Allergic Disorders.

Allergic diseases are a major health concern worldwide. Pollens are important triggers for allergic rhinitis, conjunctivitis and asthma. Proteases released upon pollen grain hydration appear to play a major role in the typical immunological and inflammatory responses that occur in patients with allergic disorders. In this study, we aimed to identify specific proteolytic activity in a set of pollens with diverse allergenic potential. Diffusates from Chenopodium album, Plantago lanceolata and Eucalyptus globulus were added to a confluent monolayer of Calu-3 cells grown in an air-liquid interface system. We identified serine proteases and metalloproteinases in all pollen diffusates investigated. Proteases found in these pollen diffusates were shown to compromise the integrity of the lung epithelial barrier by disrupting transmembrane adhesion proteins E-cadherin, claudin-1 and Occludin, as well as, the cytosolic complex zonula occludens-1 (ZO-1) resulting in a time-dependent increase in transepithelial permeability. Tight junction disruption and increased transepithelial permeability facilitates allergen exposure to epithelial sub-layers contributing to the sensitization to a wide range of allergens. These pollen extracts also induced an increase in the release of interleukin 6 (IL-6) and interleukin 8 (IL-8) cytokines measured by flow cytometry possibly as a result of the activation of protease-activated receptors 2 (PAR-2).

Recent highlights of Chinese herbs in treatment of allergic disease: Acting via mitogen-activated protein kinase signal pathway.

The histamine receptor antagonists in the treatment of allergic disease have limitations. The treatments of Chinese herbs have some curative effects on allergic skin lesions. Present research indicates that the mitogen-activated protein kinase (MAPK) signaling pathway might be equally important in allergic reactions. It was found that the inhibition of MAPK signaling pathways might relieve allergy symptoms, and some herbs can inhibit the MAPK pathway, which yields anti-allergy effects. Chinese medicines (CMs) have immense potential in the development of treatments for allergic disease.

Quantitative Polymerase Chain Reaction Analysis of the Mouse Cyp2j Subfamily: Tissue Distribution and Regulation.

Members of the cytochrome P450 CYP2J subfamily are expressed in multiple tissues in mice and humans. These enzymes are active in the metabolism of fatty acids to generate bioactive compounds. Herein we report new methods and results for quantitative polymerase chain reaction (qPCR) analysis for the seven genes (Cyp2j5, Cyp2j6, Cyp2j8, Cyp2j9, Cyp2j11, Cyp2j12, and Cyp2j13) of the mouse Cyp2j subfamily. SYBR Green primer sets were developed and compared with commercially available TaqMan primer/probe assays for specificity toward mouse Cyp2j cDNA, and analysis of tissue distribution and regulation of Cyp2j genes. Each TaqMan primer/probe set and SYBR Green primer set were shown to be specific for their intended mouse Cyp2j cDNA. Tissue distribution of the mouse Cyp2j isoforms confirmed similar patterns of expression between the two qPCR methods. Cyp2j5 and Cyp2j13 were highly expressed in male kidneys, and Cyp2j11 was highly expressed in both male and female kidneys. Cyp2j6 was expressed in multiple tissues, with the highest expression in the small intestine and duodenum. Cyp2j8 was detected in various tissues, with highest expression found in the skin. Cyp2j9 was highly expressed in the brain, liver, and lung. Cyp2j12 was predominately expressed in the brain. We also determined the Cyp2j isoform expression in Cyp2j5 knockout mice to determine whether there was compensatory regulation of other Cyp2j isoforms, and we assessed Cyp2j isoform regulation during various inflammatory models, including influenza A, bacterial lipopolysaccharide, house dust mite allergen, and corn pollen. Both qPCR methods detected similar suppression of Cyp2j6 and Cyp2j9 during inflammation in the lung.

The effects of nodakenin on airway inflammation, hyper-responsiveness and remodeling in a murine model of allergic asthma.

CONTEXT: Nodakenin is a major coumarin glucoside in the root of Peucedanum decursivum Maxim, a commonly used traditional Chinese medicine for the treatment of asthma and chronic bronchitis for thousands of years. OBJECTIVE: In this work, the anti-asthma potential of nodakenin was studied by investigation of its effect to suppress airway inflammation, hyper-responsiveness and remodeling in a murine model of chronic asthma. MATERIALS AND METHODS: BALB/c mice sensitized to ovalbumin (OVA) were challenged with aerosolized OVA for 8 weeks, orally administered with nodakenin at doses of 5, 10 and 20 mg/kg before each OVA challenge. RESULTS: Compared with the model group, nodakenin treatment markedly inhibited airway inflammation, hyper-responsiveness and remodeling, showing improvement in subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia, and decreased levels of interleukin (IL)-4, IL-5, IL-13 and matrix metalloproteinase-2/-9 in bronchoalveolar lavage fluid, and the level of OVA-specific IgE in serum. In addition, the NF-κB DNA-binding activity in lung tissues was also reduced by nodakenin treatment. CONCLUSIONS: These data indicated that nodakenin might mitigate the development of chronic experimental allergic asthma.

Chlorogenic acid alters the biological characteristics of basophil granulocytes by affecting the fluidity of the cell membrane and triggering pseudoallergic reactions.

It is not clear whether pseudoallergic reactions are caused by similar mechanisms as type I allergic reactions. 3­Caffeoylquinic acid (chlorogenic acid) is an active ingredient in traditional Chinese medicines used for antibacterial, anti-inflammatory and cholagogic purposes. It is assumed to be the reason for the high allergic reaction rates associated with certain traditional Chinese medicine injection solutions. The aim of the present study was to investigate the possible mechanisms through which chlorogenic acid triggers pseudoallergic reactions. The fluidity of the cell membrane was investigated using fluorescence recovery after photobleaching. Western blot analysis was used to measure the phosphorylation levels of the Spleen tyrosine kinase (Syk) protein and Fluo­3/AM fluorescent probes were used to investigate the influx of calcium ions. In addition, fluorescence microscopy and phalloidin were used to determine F­actin depolymerization levels. The secretion rate of ß­hexosaminidase by RBL­2H3 cells clearly increased following treatment with chlorogenic acid and the levels of cytoskeletal disintegration were also markedly increased. Furthermore, we detected an increase in the intracellular calcium ion concentration along with distinct changes in Syk protein phosphorylation and cellular F­actin. These changes indicated that chlorogenic acid affected the restructuring of the cytoskeleton and played a role in cell degranulation. In conclusion, chlorogenic acid may lead to the aggregation of lipid rafts on the cell membrane surface by altering RBL­2H3 cell membrane fluidity, thus triggering Syk­related signal transduction and inducing a truncated type I like allergic reaction.

RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents.

Genetic mutation and pharmacological inhibition of Bruton's tyrosine kinase (Btk) both have been shown to prevent the development of collagen-induced arthritis (CIA) in mice, providing a rationale for the development of Btk inhibitors for treating rheumatoid arthritis (RA). In the present study, we characterized a novel Btk inhibitor, 6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one (RN486), in vitro and in rodent models of immune hypersensitivity and arthritis. We demonstrated that RN486 not only potently and selectively inhibited the Btk enzyme, but also displayed functional activities in human cell-based assays in multiple cell types, blocking Fcε receptor cross-linking-induced degranulation in mast cells (IC(50) = 2.9 nM), Fcγ receptor engagement-mediated tumor necrosis factor α production in monocytes (IC(50) = 7.0 nM), and B cell antigen receptor-induced expression of an activation marker, CD69, in B cells in whole blood (IC(50) = 21.0 nM). RN486 displayed similar functional activities in rodent models, effectively preventing type I and type III hypersensitivity responses. More importantly, RN486 produced robust anti-inflammatory and bone-protective effects in mouse CIA and rat adjuvant-induced arthritis (AIA) models. In the AIA model, RN486 inhibited both joint and systemic inflammation either alone or in combination with methotrexate, reducing both paw swelling and inflammatory markers in the blood. Together, our findings not only demonstrate that Btk plays an essential and conserved role in regulating immunoreceptor-mediated immune responses in both humans and rodents, but also provide evidence and mechanistic insights to support the development of selective Btk inhibitors as small-molecule disease-modifying drugs for RA and potentially other autoimmune diseases.

[Skin resorptive effect of petroleum on some biochemical and immunological parameters in experimental animals].

Petroleum and its transformation products accumulated in soil along multiple trophic chains enter the human body, which increases the risk of environmentally induced diseases. A thirty-day experiment studied the cutaneous effect of different doses (4250, 850, and 425 mg/kg) of sunflower oil-emulsified petroleum. Its sensitizing and allergic effects were studied on albino guinea pigs. The activity of N-acetyl-beta-D-glucosaminidase and catalase was determined in the sera of non-inbred male albino rats. Petroleum given in a dose of 4250 mg/kg was found to have a negative effect. When its bioeffect occurred, a protective adaptive response of the body revealed in early stages gave way to tension of its adaptive capacities.

[Enhanced serum DNAase activity in hypersensitization to pollen allergens].

Factor analysis of cross-sensitization to 24 common allergens and correlation analysis of the relationship between the hypersensitivity to the allergens and some biochemical markers (the intensity of serum chemiluminescence, the content of SH-groups, and the activity of lysosomal enzymes) of the health status were carried out in a sample of Moscow residents with allergic diseases. A significant correlation was found between the serum levels of specific IgE antibodies to pollen allergens and the activity of serum acid DNAase (R = 0.498; p = 0.009; N = 67). The revealed regularity may be used to devise a test for the differential diagnosis of pollenoses and suggests that there are possible differences in the levels of apoptosis and cytogenetic damages between patients with pollenoses and those with other allergic diseases.

Prostaglandin modulation of airway inflammation and hyperresponsiveness in mice sensitized without adjuvant.

As adjuvant during sensitization may cause unspecific immune reactions, the aim of the present study was to define the role of cyclooxygenase (COX) activity on airway inflammation and airway hyperresponsiveness (AHR) in an adjuvant-free allergic mouse model. Administration of diclofenac and indomethacin (non-selective COX inhibitors), FR122047 (COX-1 inhibitor) and lumiracoxib (selective COX-2 inhibitor) enhanced AHR. Only diclofenac and lumiracoxib reduced the inflammatory cell content of bronchoalveolar lavage (BAL). Moreover, levels of prostaglandins in BAL were reduced by indomethacin and FR122047 but were unaffected by lumiracoxib. However, compared with antigen controls, none of the COX inhibitors displayed major effects on the production of cytokines, smooth muscle mass, number of goblet cells and eosinophils, or collagen deposition in the airways. These data in mice sensitized without adjuvant support the fact that COX products have a general bronchoprotective role in allergic airway inflammation. Furthermore, the data suggest that COX-1 activity predominantly generates prostanoids in BAL, whereas COX-2 activity is associated with the accumulation of inflammatory cells in BAL. This study further supports that AHR on the one hand, and the inflammatory response and generation of prostanoids on the other, are dissociated and, at least in part, uncoupled events.

NADPH oxidase activity in allergenic pollen grains of different plant species.

Pollen is an important trigger of allergic diseases. Recent studies have shown that ragweed pollen NAD(P)H oxidase generates reactive oxygen species (ROS) and plays a prominent role in the pathogenesis of allergies in mouse models. Here, we demonstrated that allergenic pollen grains showed NAD(P)H oxidase activity that differed in intensity and localization according to the plant families. The activity occurred at the surface or in the cytoplasm in pollen of grasses, birch, and ragweed; in subpollen particles released from ragweed pollen; and at the inner surface or in the cytoplasm but not on the outer wall, which was sloughed off after the rupture, of pollen of Japanese cedar and Japanese cypress. The activity was mostly concentrated within insoluble fractions, suggesting that it facilitates the exposure of tissues to ROS generated by this enzyme. The extent of exposure to pollen-generated ROS could differ among the plant families.

A pollen-specific polygalacturonase from lily is related to major grass pollen allergens.

A pollen-specific gene from lily (Lilium longiflorum Thunb. cv. Snow Queen), designated LLP-PG, was characterized. Southern blots of lily genomic DNA indicated that LLP-PG is a member of a small gene family. A thorough sequence analysis revealed that the LLP-PG gene is interrupted by two introns and encodes a protein of 413 amino acids, with a calculated molecular mass of 44 kDa, and a pI of 8.1. Evaluation of the hydropathy profile showed that the protein has a hydrophobic segment at the N-terminus, indicating the presence of a putative signal peptide. A sequence similarity search showed a significant homology of the encoded protein to pollen polygalacturonases (PGs) from various plant species and to an important group (group 13) of grass pollen allergens. The LLP-PG transcript is pollen-specific and it accumulates only at the latest stage during pollen development, in the mature pollen. In contrast to other "late genes" LLP-PG transcript can neither be induced by abscisic acid (ABA) nor by dehydration. Immunoblot analyses of pollen protein extracts from lily, timothy grass and tobacco with IgG antibodies directed against LLP-PG and against the timothy grass pollen allergen, Phl p 13, indicated that lily LLP-PG shares surface-exposed epitopes with pollen PGs from monocotyledonous and dicotyledonous plants. Enzyme-linked immunosorbent assay (ELISA) analyses and inhibition ELISA assays with patients' IgE demonstrated a very low IgE reactivity of lily rLLP-PG and a lack of cross-reactivity between rLLP-PG and the timothy grass pollen allergen, rPhl p 13. These data demonstrated that despite the significant sequence homology and the conserved surface-exposed epitopes LLP-PG represents a low-allergenic member of pollen PGs.

IL-converting enzyme/caspase-1 inhibitor VX-765 blocks the hypersensitive response to an inflammatory stimulus in monocytes from familial cold autoinflammatory syndrome patients.

Familial cold autoinflammatory syndrome (FCAS) and the related autoinflammatory disorders, Muckle-Wells syndrome and neonatal onset multisystem inflammatory disease, are characterized by mutations in the CIAS1 gene that encodes cryopyrin, an adaptor protein involved in activation of IL-converting enzyme/caspase-1. Mutations in cryopyrin are hypothesized to result in abnormal secretion of caspase-1-dependent proinflammatory cytokines, IL-1beta and IL-18. In this study, we examined cytokine secretion in PBMCs from FCAS patients and found a marked hyperresponsiveness of both IL-1beta and IL-18 secretion to LPS stimulation, but no evidence of increased basal secretion of these cytokines, or alterations in basal or stimulated pro-IL-1beta levels. VX-765, an orally active IL-converting enzyme/caspase-1 inhibitor, blocked IL-1beta secretion with equal potency in LPS-stimulated cells from FCAS and control subjects. These results further link mutations in cryopyrin with abnormal caspase-1 activation, and support the clinical testing of caspase-1 inhibitors such as VX-765 in autoinflammatory disorders.

1,3-beta-glucanases as candidates in latex-pollen-vegetable food cross-reactivity.

BACKGROUND: 1,3-beta-glucanases (group 2 of pathogenesis-related proteins) are enzymes widely distributed among higher plants and have been recently proven to be significant allergens. OBJECTIVE: The aim of this work was to study the potential implication of 1,3-beta-glucanases in cross-reactivities among latex, pollen and vegetable foods. METHODS: The cDNA encoding the N-terminal domain (NtD) of Ole e 9, a major allergenic 1,3-beta-glucanase from olive pollen, was amplified by polymerase chain reaction and produced as a recombinant protein in Pichia pastoris (recombinant N-terminal domain, rNtD). Circular dichroism, ELISA, immunoblotting and immunoblotting inhibition experiments were carried out. Sera from olive pollen allergic patients and a rNtD-specific polyclonal antiserum were used. RESULTS: The NtD of Ole e 9 has been produced at high yield in the yeast P. pastoris and possesses 1,3-beta-glucanase activity. The expressed polypeptide conserves IgE and IgG immunodominant epitopes of the whole Ole e 9. A rNtD-specific polyclonal antiserum and sera from olive pollen allergic patients allowed detection of IgG and IgE reactive peptidic epitopes common to 1,3-beta-glucanase Ole e 9 in extracts from ash and birch pollen, tomato, potato, bell-pepper, banana and latex. CONCLUSION: rNtD and homologous glucanases are new molecules to be used in diagnostic protocols as they could help to identify allergic pollen patients who are at risk for developing allergic symptoms to fruits, vegetables and latex.

Anti-allergic effects of Artemisia iwayomogi on mast cell-mediated allergy model.

The discovery of drugs for the treatment of allergic disease is an important subject in human health. The Artemisia iwayomogi (Compositae) (AIE) has been used as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. In this report, we investigated the effect of AIE on the mast cell-mediated allergy model and studied the possible mechanism of action. AIE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. AIE decreased immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis (PCA) reaction. AIE dose dependently attenuated histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. AIE decreased the compound 48/80-induced intracellular Ca(2+). Furthermore, AIE decreased the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 gene expression and production in human mast cells. The inhibitory effect of AIE on the proinflammatory cytokine was p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) dependent. AIE attenuated PMA plus A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB and specifically blocked activation of p38 MAPK but not that of c-jun N-terminal kinase and extracellular signal-regulated kinase. Our findings provide evidence that AIE inhibits mast cell-derived immediate-type allergic reactions and involvement of intracellular Ca(2+), proinflammatory cytokines, p38 MAPK, and NF-kappaB in these effects.

The biochemical, molecular, and genomic aspects of leukotriene C4 synthase.

Leukotriene C4 (LTC4) synthase is an 18 kD integral membrane enzyme of the 5-lipoxygenase/LTC4 synthase pathway and is positioned as the pivotal and only committed enzyme for the formation of the cysteinyl leukotrienes. Although its function is to conjugate catalytically LTA4 to reduced glutathione, LTC4 synthase is differentiated from other glutathione S-transferase family members by its lack of amino acid homology, substrate specificity, and kinetics. LTC4 synthase (LTC4S) protein is present in the perinuclear membranes of a limited number of hematopoietic cells involved in allergic inflammation, including mast cells, eosinophils, basophils, and macrophages. The cDNA encodes a monomeric protein of 150 amino acids with three hydrophobic domains interspersed with two hydrophilic loops. Site-directed mutagenic studies reveal that the enzyme functions as a homodimer and that arginine-51 in the first hydrophilic loop, and tyrosine-93 in the second hydrophilic loop, are involved in the acid and base catalysis of LTA4 and glutathione, respectively. Homology and secondary structural predictions indicate that LTC4S is a novel member of a new gene superfamily of integral membrane proteins, each with the capacity to participate in leukotriene biosynthesis. The gene for LTC4S is 2.5 kb in length and is localized on chromosome 5q35, distal to that of the genes for cytokines and receptors important in the development and perpetuation of allergic inflammation. Immunohistochemical studies of mucosal biopsies from the bronchi of aspirin-intolerant asthmatics show that LTC4S is overrepresented in individuals with this phenotype, and this finding correlates with overproduction of cysteinyl leukotrienes and lysine-aspirin bronchial hyperreactivity.

Antioxidant enzymatic activities in human blood cells after an allergic reaction to pollen or house dust mite.

Several diseases have been related to oxidative stress. Recently, antioxidant functions have also been linked to anti-inflammatory properties. Cell defenses against reactive oxygen species include antioxidant enzymes. We studied the enzymatic antioxidant capacity in human blood of both red blood and mononuclear cells from patients suffering from an allergic reaction to pollen or house dust mite. We determined superoxide dismutases (SODs), glutathione peroxidase (GSHPx) and catalase (CAT) activities in each cell type. We also determined the extent of thiobarbituric acid reactive substances (TBARS), in order to study the correlation between the cellular enzymatic activities, the redox status and the disease. In mononuclear cells from allergic patients, SODs and CAT activities were enhanced compared to controls. Conversely, a decrease in GSHPx activity was found. In erythrocytes, higher values for GSHPx and SODs and similar CAT activities were found in allergic patients and controls. Interestingly, CuZnSOD and MnSOD activities were enhanced in the same proportion for both, erythrocytes and mononuclear cells. TBARS were also enhanced in both types of cells. The respective enzymatic imbalances in mononuclear cells and erythrocytes, namely, GSHPx/SOD and CAT/SOD, and their consequences are discussed. To our knowledge, this is the first global study of antioxidant enzymes, including TBARS level determinations, in allergy.

Increased myosin light chain kinase content in sensitized canine saphenous vein.

Our previous studies revealed that smooth muscle from sensitized canine saphenous vein (SCSV) demonstrated greater active shortening capacity, maximum shortening velocity, and prolonged relaxation vis-a-vis the control muscle. These changes could be responsible for the in vivo hyperreactivity of venous smooth muscle observed in anaphylactic shock. Because smooth muscle cross-bridge cycling is regulated by myosin light chain kinase (MLCK)-dependent phosphorylation of the 20-kDa myosin light chain (MLC20), we studied MLC20 and MLCK phosphorylation in homogenates of SCSV and veins from littermate control dogs. We found that phosphorylation of MLC20 in SCSV homogenate was higher (42.26 +/- 5.10%) compared with control homogenates (26.69 +/- 3.30%; P < 0.05); MLCK content was significantly higher in SCSV homogenates [0.169 +/- 0.019 (SE) mu g/mg protein] than in control homogenates (0.075 +/- 0.004 mu g/mg protein; P < 0.05). Total MLCK activity increased from 6.16 +/- 0.60 x 10(-5) nmol Pi x mg fresh weight of tissue-1 x min-1 in control homogenates to 12.50 +/- 2.50 x 10(-5) nmol Pi x mg fresh weight of tissue-1 x min-1 in sensitized homogenates (P < 0.05). Specific MLCK activity was, however, similar in sensitized and control homogenates. The results of our study suggest that elevation of MLCK content in the homogenate could account for the increased contractility of the SCSV in anaphylactic shock.

Proteinases from pollen and pests.

An examination of the proteinases present in two very different systems is described, in order to illustrate the diversity in function of this class of enzymes. In the first case we have noted the importance of gut proteinases from the fire ant Solenopsis invicta in relation to the nutritional requirements of the entire colony. In the second we have investigated the properties of endoproteases from both ragweed and mesquite pollen, relative to their role in the development of allergies and asthma. If the function of each type of enzyme(s) is correct, then it is clear that addition of exogenous inhibitors might be useful in a) controlling the infestation associated with the fire ant, and b) reducing the deleterious effects associated with the development of asthma.

Biochemical abnormalities in patients with multiple chemical sensitivities.

Patients with MCS show numerous physiological and biochemical abnormalities and are generally sicker than a control group of allergic patients. Associated with MCS are mitral valve prolapse, hypothyroidism, autoimmune thyroiditis, specific abnormalities of amino acid and essential fatty acid metabolism, and diminished activity of ESOD and EGPx. Equally prevalent among MCS patients and controls are deficiencies of magnesium and Vitamin B6. Since patients with MCS feel sick almost all of the time, it is likely that some of these abnormalities contribute to their general level of ill health, if not to their sensitivities. It is also possible that these various abnormalities are caused by some unidentified fundamental metabolic or neuroendocrine disturbance that is common to states of hypersensitivity. A provocative finding is the high frequency with which impaired anti-oxidant levels were detected. Erythrocyte activity of SOD was low in 89% and EGPx was low in 48% of MCS patients. Furthermore, 41% showed impaired excretion of essential amino acids, despite a high protein diet, and leucocyte vitamin C was low in the 5 patients not taking vitamin C supplements. Anti-oxidant deficiences may certainly contribute to hypersensitivity to environmental pollutants and toxic chemicals. In fact, treatment with anti-oxidants, including selenium, vitamin C, copper, zinc, and sulfur-containing amino acids was associated with major clinical improvement in 14 (25%) of the patients in the MCS group and with limited relief of symptoms in another 10 (18%). In all patients in whom ESOD or EGPx were repeated, improvement in levels was observed following treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased requirements for essential fatty acids in atopic individuals: a review with clinical descriptions.

Patients with atopic eczema and a mixture of allergic illnesses show biochemical evidence suggesting impairment in the desaturation of linoleic acid and linolenic acid by the enzyme delta-6 dehydrogenase. Consequences of this enzyme defect are 1) diminished synthesis of the 20-carbon polyunsaturated fatty acids, which are prostaglandin precursors and 2) a reduction in the concentration of double bonds in the cell membrane. A distortion in the production of prostaglandins and leukotrienes, which might result from this block, can account for the immunological defects of atopy and a variety of clinical symptoms experienced by atopic individuals. Dietary supplementation with essential fatty acids relieves the signs and symptoms of atopic eczema, may improve other types of allergic inflammation, and may also correct coexisting symptoms as diverse as excessive thirst and dysmenorrhea. Further research is suggested to test the hypothesis that some atopic states represent a condition of essential fatty acid dependency owing to defective desaturation of dietary fatty acids.