Dysregulation of murine immune functions on inhalational exposure to ammonia, dimethyl disulfide, 3-methylindole, or propionic acid.

Animal husbandry workers are exposed to various malodorous compounds in the workplace. Although these compounds cause severe nuisance, no systemic investigation of their effects on the immune system has been conducted. To address this issue, we evaluated the effects of inhalational exposure to ammonia, dimethyl disulfide, 3-methylindole (3-MI), and propionic acid (PA), representing four major groups of malodorous compounds, on humoral and cellular immunity in mice. Mice were exposed to the substances (low dose: 10 µL and high dose: 200 µL) for 10 min/day for 4 weeks in a modified standard mouse cage. Neutrophil% and splenic cytotoxic T cell% were significantly lower in the high-dose ammonia group than in the vehicle control. Exposure to ammonia and 3-MI increased immature thymic T lymphocyte% relative to control and concomitantly decreased both mature helper and cytotoxic T-cell populations in the thymus. In the ammonia exposure group, levels of serum immunoglobulin E and immunoglobulin A were elevated, and the IgG2a:IgG1 ratio in the serum was reduced in a dose-dependent manner. Splenic natural killer cell activity was significantly less in the PA exposure group than in the control. Overall, our findings suggest that inhalational exposure to these malodorous substances disturbs immune homeostasis in vivo.

Inflammation and hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with both acute and chronic liver dysfunction, spanning a spectrum that ranges from mild neuropsychological disturbances to coma. The central role of ammonia in the pathogenesis of HE remains incontrovertible however, there is a robust evidence base indicating the important role of inflammation in exacerbating the neurological effects of HE. Inflammation can arise directly within the brain itself as a result of deranged nitrogen and energy homeostasis, with resultant neuronal, astrocyte and microglial dysfunction. Inflammation may also originate in the peripheral circulation and exert effects on the brain indirectly, via the release of pro-inflammatory mediators which directly signal to the brain via the vagus nerve. This review summarises the data that demonstrate the synergistic relationship of inflammation and ammonia that culminates in the manifestation of HE. Sterile inflammation arising from the inflamed or necrotic liver, circulating endotoxin arising from the gut (bacterial translocation) inducing immune dysfunction, and superimposed sepsis will be comprehensively discussed. Finally, this review will provide an overview of the existing and novel treatments on the horizon which can target the inflammatory response, and how they might translate into clinical practise as therapies in the prophylaxis and treatment of HE.

Effect of environmental parameters on immune response of the Indian spiny lobster, Panulirus homarus (Linnaeus, 1758).

The high export value of the Indian spiny lobster Panulirus homarus increasingly attracts the aquaculturists for farming and fattening. However, lack of knowledge on the effect of environmental parameters on the immune system of this animal could result in high mortality, which ultimately may cause major loss to the industry. Here, we report the effect of salinity (20, 25, 35, 40, and 45 per thousand), pH (5.0, 8.0, and 9.5), dissolved oxygen (DO) (1 and 5 mg L(-1)), and ammonia-N concentration (0, 0.5, 1.5 and 3 mg L(-1)) on the immune response of P. homarus measured in the haemolymph in terms of Total Haemocyte Count (THC), phenoloxidase (PO) activity, and NBT-reduction. Our data showed significant reduction (P<0.05) in THC, and NBT-reduction at lower (20 per thousand) and higher (45 per thousand) salinities. However, PO activity showed significant disparity, showing an increasing trend from 20 to 45 per thousand. Significant reduction (P<0.05) in THC and PO activity under acidic and alkaline conditions, under hypoxic condition (1 mg L(-1)), and at the higher ammonia-N concentrations than their respective optimal conditions were observed. Thus, suggesting that extreme environmental parameters can induce modifications in the immune system of the spiny lobster P. homarus, which may enhance their susceptibility to opportunistic pathogens. The humoral parameters such as THC, PO activity, and NBT-reduction can be used as potential stress indicators for healthy management of spiny lobsters.

Excretion of ammonia by Lucilia cuprina larvae suppresses immunity in sheep.

Attempts to immunise sheep against natural infestations by Lucilia cuprina larvae have not been effective. Yet it is known that the larvae excrete the immunosuppressant ammonium bicarbonate. The effect of larval ammonium and nonionic ammonia on immunopathobiology was evaluated in 12 infested sheep. The concentration of ammonium in veins draining infested sites was measured in another group of four sheep. Mean jugular unionized ammonia concentration increased 3.5 to 5.6 times above pre-infested control levels. Mean venous ammonium concentrations draining infested sites were 13 times higher than pre-infested jugular or carotid levels. Increases in jugular ammonia concentrations correlated with increased number of larvae, area of infestation, earlier death, neutropenia, eosinopenia, lymphocytopenia, large declines in serum globulins and zinc, and large rises in toxic neutrophils. The high concentrations of toxic unionized ammonia in blood directly permanently damaged neutrophils and lymphocytes and depressed serum globulin production. The results show that the ammonium from the excreta of larvae of L. cuprina may be highly immunosuppressive.

The allergenic properties of fresh and preserved Hevea brasiliensis latex protein preparations.

The allergenic properties of the proteins of two lyophilized fractions of fresh natural rubber latex obtained by ultracentrifugation, the C serum and the sedimented bottom or lutoid fraction, have been compared with those of the serum proteins of two samples of high ammonia latex (HAL) [A]HALS obtained from HAL stored for more than 1 year, and [M]HALS derived from HAL stored for 6 weeks before ultracentrifugation and lyophilization. The most potent source of allergenic polypeptides both for skin prick testing of latex-sensitive patients and for immunoblots of their blood serum was the lutoid fraction of fresh latex. Skin prick tests and immunoblots of patients' sera showed that the allergenicity of the ammoniated latex decreased during storage. Skin prick tests using fractions of [A]HALS, C serum and lutoid proteins obtained after passage through a Sephacryl S300 column showed that the components of all three preparations which eluted in the largest volumes were almost equally effective in provoking the largest number of responses. Immunoblots of the sera of 43 latex-sensitive individuals showed that the majority (66%) of sera of the adult allergic patients reacted with a polypeptide of 19 kD. No characteristic pattern of binding latex polypeptides could be recognized in the sera from patients who were also asthmatic or from those who had an anaphylactic response to latex proteins.

Serologic methods in the laboratory diagnosis of latex rubber allergy: study of nonammoniated, ammoniated latex, and glove (end-product) extracts as allergen reagent sources.

In the absence of approved natural rubber latex skin testing reagents, serologic methods for the detection of latex-specific immunoglobulin E (IgE) antibody are useful in the definitive diagnosis of latex allergy. In this study we examined extracts from two nonammoniated latex (NAL), two ammoniated latex (AL), and three diverse latex rubber gloves as sources of allergen for their utility in solid phase radioimmunoassays (SPRIAs) for latex-specific IgE. Serum samples were collected from 46 healthcare workers (HCWs), one beautician, two clerks, and seven children with spina bifida who exhibited clinical evidence of latex-associated contact dermatitis (CD, n = 8), contact urticaria (CU) with or without CD (n = 15), or systemic reactions involving respiratory symptoms with or without anaphylaxis (n = 33) and from 10 latex-exposed HCW control subjects with no latex allergy symptoms. Serum samples were coded and analyzed in a blinded manner in two laboratories by three particulate and four nonparticulate SPRIAs with different latex extracts on the allergosorbent. Intraassay coefficient of variation as assessed with 44 split, randomized, blinded serum specimens was < 20%. Agreement within a source of latex (e.g., NAL, AL, or gloves) and between laboratories was > 90% concordant for Glove 1/Glove 2 and NAL1/2. Specific IgE antilatex was detected in one of 10 latex-exposed control serum samples by five of the seven SPRIAs, despite a lack of clinical evidence for latex allergy in this otherwise atopic individual. Latex-specific IgE was detected in the serum of 22% of subjects with CU with or without CD, suggesting that IgE antibody may not be the primary factor involved in the induction of these local reactions. Approximately two thirds of the systemic reactor group had detectable latex-specific IgE in their serum, with levels ranging from 0.7 to 338 ng/ml. The predictive characteristics of these assays will await future provocation testing. We conclude that glove extracts contain as complete a repertoire of allergens as the NAL and AL. Of the three source latex materials, NAL and glove extracts provided the most sensitive and greatest consistency of IgE antibody results between laboratories.