Hypersensitive Dogs Research Articles

Inhibitory effect of topical adelmidrol on antigen-induced skin wheal and mast cell behavior in a canine model of allergic dermatitis.

BackgroundAdelmidrol is a semisynthetic derivative of azelaic acid and analogue of the anti-inflammatory compound palmitoylethanolamide (PEA). Based upon its physicochemical properties, adelmidrol is suitable for topical application. The main objective of the present study was to evaluate the efficacy of a topical adelmidrol emulsion on early and late inflammatory responses in hypersensitive dogs. Repeated intradermal injections of Ascaris suum extract were performed in both lateral thoracic areas of six conscious hypersensitive Beagle dogs, topically treated during 8 consecutive days. Adelmidrol (2%) was applied to one side and vehicle to the other. 24 hours after the last antigen challenge, two biopsies (adelmidrol- and vehicle-treated side) were obtained for each dog at the antigen injection site.ResultsA significant reduction in the antigen-induced wheal areas was observed on the 4th and 7th day of adelmidrol treatment. Moreover, cutaneous mast cell numbers were significantly decreased in biopsies obtained after 8 consecutive days of topical adelmidrol treatment.ConclusionsThe results obtained in the present study show that topical treatment with adelmidrol might represent a new therapeutic tool in controlling the early and late allergic inflammatory skin responses in companion animals.

Effects of palmitoylethanolamide on the cutaneous allergic inflammatory response in Ascaris hypersensitive Beagle dogs

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with anti-inflammatory and anti-hyperalgesic properties. The main objective of the present study was to evaluate the effects of PEA on the cutaneous allergic inflammatory reaction induced by different immunological and non-immunological stimuli in hypersensitive dogs. Six spontaneously Ascaris hypersensitive Beagle dogs were challenged with intradermal injections of Ascaris suum extract, substance P and anti-canine IgE, before and after a single oral administration of PEA at doses of 3, 10 and 30 mg/kg. A significant reduction in wheal area induced by both antigen and anti-canine IgE challenge was observed after PEA administration. No significant differences were observed between the two higher doses studied, suggesting that the 10 mg/kg dose had exerted the maximum inhibitory effect. When blood levels of PEA were compared with the effects at different times, an evident correlation was obtained. However, the anti-inflammatory effects of PEA were more long-lasting than their plasma concentrations. The intradermal injection of substance P did not reveal any skin reaction (wheal or erythema formation) at any of the concentrations tested. In conclusion, PEA might constitute a new therapeutic strategy for the treatment of allergic inflammatory skin diseases in companion animals.

Patch testing of experimentally sensitized beagle dogs: development of a model for skin lesions of atopic dermatitis

In humans with atopic dermatitis (AD), the epicutaneous application of allergens (atopy patch tests or APT) to which the patients are sensitized often results in the development of inflammation resembling that of spontaneous skin lesions. Dogs are affected with a natural homologue of human AD, but information on the induction of positive patch testing reactions is limited. The objectives of this pilot study were to determine the nature and cellular dynamics of inflammation occurring after APT in dogs hypersensitive to house dust mite and flea allergens. Laboratory Beagles were sensitized experimentally to Dermatophagoides farinae house dust mites (two dogs), Ctenocephalides felis flea saliva (one dog) or both (two dogs). Two other dogs served as nonsensitized controls. Both allergens and saline were applied epicutaneously. Macroscopic evaluations and skin biopsies were performed at 4, 24, 48 and 96 h after starting allergenic challenge. Biopsies were evaluated histologically and immunohistochemically with a panel of monoclonal antibodies specific for canine leucocyte antigens. Positive macroscopic reactions consisted of erythema, oedema and induration, and they occurred between 24 and 96 h after allergen application. Macroscopic and microscopic APT reactions developed only whenever serum IgE was present against tested allergens. Microscopically, positive APT was associated with epidermal hyperplasia, Langerhans' cell hyperplasia, and eosinophil and lymphocyte epidermotropism. Dermal inflammation was mixed and arranged in a superficial perivascular to interstitial pattern. Numerous IgE+-CD1+ dendritic cells and gamma-delta T-lymphocytes were observed. Macroscopically and microscopically, APT reactions in these experimentally sensitized animals resembled those seen in lesional biopsy specimens of dogs and humans with spontaneous AD. Therefore, APT in hypersensitive dogs provides a relevant experimental model to investigate the pathogenesis and treatment of both canine and human AD skin lesions.

Pilot investigation of a model for canine atopic dermatitis: environmental house dust mite challenge of high‐IgE–producing beagles, mite hypersensitive dogs with atopic dermatitis and normal dogs

Although canine atopic dermatitis (cAD) is common, few models are available. The aim of this study was to evaluate high-IgE beagles epicutaneously sensitized to house dust mite (HDM) as a possible model for cAD. Six high-IgE beagles were environmentally challenged with HDM using various doses and protocols. Similar challenge protocols were used in positive and negative control dogs: three dogs with naturally occurring cAD and positive intradermal skin test (IDT) to HDM and three normal dogs without history of skin disease and negative IDT to HDM. All high-IgE beagles and all atopic dogs developed severe cutaneous lesions and pruritus after challenge. Lesions were erythematous papules and macules in contact areas such as face, ears, ventral abdomen, groin, axillae and feet. They were first visible after 6 h and increased in severity over time. No normal dog developed pruritus or lesions. Biopsies of representative lesions in the high-IgE beagles were taken for histopathology and immunohistochemistry. There was superficial perivascular dermatitis with mononuclear infiltrates and spongiosis. Lymphocytes and eosinophils accumulated in small epidermal micro-abscesses with hyperplasia of epidermal IgE-bearing dendritic cells. These findings suggest that this colony of high-IgE beagles develops a dermatitis that clinically, histopathologically and immunologically resembles the naturally occurring canine disease. It is also concluded that this modality of challenge is not irritating to normal dogs but induces flare-ups in hypersensitive atopic dogs.

Futtermittelhypersensitivitäts-Dermatitis beim Hund: Möglichkeiten der Diagnose

Dogs with food hypersensitivity usually develop chronic pruritic dermatoses virtually indistinguishable from atopic dermatitis. These reactions are often called food allergy but the pathogenesis is poorly characterized. Several studies have addressed the incidence of canine adverse reactions to food but the outcomes were conflicting. The gold standard for the diagnosis of such a condition is the restricted dietary trial and the subsequent provocation challenge. Some attempts have been made to develop serological tests but none of these tests accurately predicted canine food sensitivity. The aim of the present study was to determine the incidence of food hypersensitivity dermatitis and to evaluate a newly developed serological test for the diagnosis of food allergy in dogs. Only 9% of 55 dogs with dermatological signs compatible with food hypersensitivity or atopic dermatitis have been diagnosed as food hypersensitive dogs. The repeatability of the serological test has shown to be insufficient.

Cutaneous Leishmaniasis in Naturally Infected Dogs is Associated with a T Helper-2-biased Immune Response

Skin lesions are a frequent manifestation of Leishmania infantum infections in Mediterranean countries. This study demonstrates by real-time reverse transcriptase-polymerase chain reaction the local cytokine response in skin biopsies from Leishmania-infected dogs (n=10). As controls, we investigated skin biopsies from healthy (n=10) and fleabite hypersensitive dogs (n=10). We established a quantitative PCR to determine the parasite burden in biopsies. The objective was to elucidate whether a correlation exists between parasite number, histologic response, and T helper-1 (TH1)/T helper-2 (TH2) cytokine expression in lesional skin of naturally infected dogs. In Leishmania-infected dogs, interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) messenger RNA production was significantly higher than controls. Furthermore, dogs with a high Leishmania burden had a significantly higher IL-4 expression, whereas no difference was noted with regard to expression of other cytokines. By comparing the pattern of inflammation and cytokine expression, a clear trend became evident in that levels of IL-4, TNF-alpha, and IFN-gamma were elevated in biopsies with a periadnexal nodular pattern and in biopsies where the severity of the periadnexal infiltrate was equal to the perivascular to interstitial infiltrate. Expression of IL-4, IL-13, and TNF-alpha was slightly increased in biopsies where plasma cells prevailed on lymphocytes, whereas expression of IFN-gamma was moderately higher when lymphocytes were predominating. In summary, the present study demonstrates that the local immune response in naturally occurring leishmaniasis includes TH1 as well as TH2 cytokine subsets. Furthermore, respective data suggest that increased expression of the TH2-type cytokine IL-4 is associated with both severe clinical signs and a high parasite burden in the skin lesions.

Use of an amplified ELISA technique for detection of a house dust mite allergen (Der f 1) in skin and coat dust samples from dogs.

To use an amplified ELISA technique to document the presence and quantify the concentration of the house dust mite allergen, Der f 1, in skin and coat dust samples collected from dogs. 29 pet dogs of various breeds. Dogs were weighed, and body surface area in square meters was determined. Skin and coat dust samples were obtained by vacuuming dogs. Collected dust was analyzed by use of standard and amplified ELISA techniques. By use of the standard ELISA technique, Der f 1 was detected in skin and coat dust samples from 6 of 29 (21%) dogs. Mean concentration of Der f 1 in the 6 samples with positive assay results was 16.16 ng/mL (range, 5.61 to 31.24 ng/mL). Samples with negative assay results were retested for dust mite allergen by use of an amplified ELISA technique; an additional 14 dogs had positive assay results. Mean concentration of allergen was 0.36 ng/mL (range, 0.19 to 2.20 ng/mL). Combining both techniques, 20 of 29 (69%) dogs had positive assay results for Der f 1. Results of our study indicate that house dust mite allergens are present on the skin and in the coat of dogs, and this source of allergen may act as a reservoir for allergen exposure in hypersensitive dogs. Use of an amplified ELISA technique to determine environmental concentrations of house dust mite allergens in homes and on dogs will help to identify the relationship between immunologic findings and environmental exposures in dogs with atopic dermatitis.

Inhibitory effects of rupatadine on mast cell histamine release and skin wheal development induced byAscaris suum in hypersensitive dogs

The present studies were performed to compare the cutaneous antiallergic effects of rupatadine, a new potent dual antagonist of histamine and platelet-activating factor (PAF), with those of loratadine (an H1-antihistamine) and SR-27417A (a PAF antagonist). Two experimental models were used: an in vivo skin challenge by Ascaris suum extract administered intradermically in conscious hypersensitive dogs and an in vitro assay of Asc S 1 antigen-induced histamine release from isolated canine skin mast cells. In antigen-induced skin inflammation, both rupatadine and loratadine administered orally inhibited wheal formation in a dose-dependent manner at the studied doses. At the 0.1 mg/kg dose, maximum inhibition values for rupatadine and loratadine were similar, but the effect of rupatadine lasted 24 h, whereas loratadine's effect disappeared after 8 h. At the 1 mg/kg dose, the two compounds behaved similarly, with maximum effects of about 65% (4 h after treatment) and activity lasting more than 24 h in both cases. At the 10 mg/kg dose, rupatadine and loratadine exhibited maximum effects of 84 and 64% in wheal inhibition 2 and 4 h after drug administration, respectively. SR-27417A did not inhibit ascaris-induced wheal at the doses studied (1 and 10 mg/kg p.o.). In isolated canine skin mast cells, rupatadine and loratadine inhibited antigen-induced histamine release in a concentration-dependent manner. Rupatadine was more potent than loratadine at each concentration studied (100 nM–30 μM). Maximum inhibitory effects were 83 and 67% for rupatadine and loratadine, respectively, after a 30 μM concentration. Rupatadine, with an IC50 value of 5.3 μM, was about fourfold more potent than loratadine, with an IC50 value of 19 μM. SR-27417A exhibited no effect in our experimental model. Moreover, neither loratadine or rupatadine showed cytotoxic or prodegranulating effects at any concentration, whereas SR-27417A was cytotoxic at the highest concentration (30 μM). Thus, rupatadine is effective in controlling inflammatory reactions in dog skin and the effect may be partly due to its modulation of mast cell degranulation, but not to its PAF-antagonist properties. Drug Dev. Res. 44:49–55, 1998. © 1998 Wiley-Liss, Inc.

Changes in cell-mediated immune responses after experimentally-induced anaphylaxis in dogs

Experimentally-induced type 1 hypersensitivities were induced in normal dogs to either ovalbumin or Ascaris antigen. In vitro and in vivo cell-mediated immune responses were measured before sensitization and again at 1 and 6 days after induction of anaphylaxis by intravenous challenge with antigen. Histamine-modulated lymphocyte functions, such as histamine-induced suppression, histamine co-mitogen induced blastogenesis and the in vivo cutaneous responses to intradermally injected mitogens decreased post anaphylaxis. Spontaneous suppression of the autologous mixed-lymphocyte reaction increased post anaphylaxis. Lymphocyte blastogenic response to Concanavalin A (Con A) decreased at 6 (but not at 1) days post anaphylaxis probably due to a mediator other than histamine. Blastogenesis of 24 h preincubated cells by suboptimal concentration of Con A, declined post anaphylaxis, but Con A-induced suppression was not significantly altered. Dogs with atopic dermatitis have some altered cell-mediated immune responses. Altered histamine-induced and spontaneous suppression, histamine suppression of mitogenesis and decreased contact sensitivity observed in this experimental type 1 hypersensitivity mimicked that of atopic dogs. Increased cutaneous response to mitogens observed in atopic dogs was not reproduced in the type 1 hypersensitive dogs. These findings suggest some of the altered cell-mediated immune functions observed in dogs with atopic dermatitis result from type 1 hypersensitivity. The other abnormalities may be intrinsic to the atopic state.

The role of allergy in the development of canine pyoderma

ABSTRACTPyoderma is commonly seen in canine veterinary practice and usually occurs as a complicating factor in other primary conditions. Allergic skin disease is often the underlying cause but the precise relationship between allergy and infection is unknown. Our studies have investigated the relationship between bacterial proliferation at the skin surface and hypersensitivity reactions with the skin. Hypersensitive dogs were shown to have significantly higher surface counts of staphylococci than normal controls and these bacteria were concentrated in the more superficial layers of the stratum corneum. Intradermal injection of staphlococcal antigens in normal dogs elicited epidermal damage similar to that seen in clinical disease. Preliminary autoradiographic studies using a model of canine skin hypersensitivity reactions showed that percutaneous absorption of radiolabelled staphylococcal antigens was increased by mast cell degranulation. These findings suggest that a major role of hypersensitivity reactions in the pathogenesis of pyoderma may be via an effect on epidermal permeability, promoting penetration of staphylococcal antigens from the stratum corneum which then cause the lesions of pyoderma. Hypersensitivity reactions may also lead to changes in the skin surface microclimate leading to increased bacterial counts on the skin surface, so exacerbating the condition.

Oral antiallergic activity in ascaris hypersensitive dogs: A study of known antihistamines and of the new compounds ramastine (R 57 959) and levocabastine (R 50 547)

AbstractThe antiallergic effectiveness of twelve compounds was studied in ascaris hypersensitive dogs by measuring allergen‐induced skin reactions before and 1, 4, 20, and 72 hr after oral treatment. The specific serotonin S2‐antagonist ritanserin at 2.5 mg/kg and the selective histamine H2‐antagonist cimetidine at 10 mg/kg did not reduce the allergic wheals. Chlorpheniramine and clemastine were inactive at 2.5 mg/kg. The remaining eight compounds studied over a wide dose range produced peak activity at markedly different doses and time intervals (hr). The lowest oral ED50‐values in mg/kg were: levocabastine: 0.0035 (4); R 57 959: 0.048 (20); astemizole: 0.13 (20); ketotifen: 0.20 (4); cyproheptadine: 0.21 (4); azatadine: 0.32 (4); oxatomide: 1.26 (20); terfenadine: 1.26 (1). The lowest oral ED50‐values in dogs and in rats (compound 48/80 lethality test) were similar, the largest difference being a fourfold potency gain of oxatomide in dogs. The short‐acting compounds in rats (azatadine, cyproheptadine, ketotifen, and terfenadine) had also a duration of action of less than 12 hr in dogs. Levocabastine, R 57 959, astemizole, and oxatomide acted more than 16 hr. Maximal inhibition of the allergic wheal volumes was highest with levocabastine (90%); it reached 80% with R 57 959 and ranged from 67 to 78% with the remaining compounds. On the basis of their activity characteristics in dogs, levocabastine and R 57 959 are potentially very effective antiallergic drugs.

Bronchoconstrictor reaction pattern of the upper respiratory tract and peripheral bronchial system

Ascaris suum hypersensitive dogs were exposed to ascaris aerosol, histamine, and acetylcholine at different time intervals separately to the upper part of the airtract and to the lower airways. Before and during the exposure the plasma histamine concentrations were measured. Acetylcholine and histamine delivered at the upper part of the airtract do not cause bronchoconstriction. Histamine diffuses in relatively high amounts through the mucosa of the upper part of the airtract into the arterial plasma. Ascaris extract causes bronchoconstriction from the upper part of the airtract as well as from the lower airways. Histamine possibly changes the diffusibility and the sensitivity of the histamine receptor. The correlation between Edyn during acetylcholine and histamine aerosol inhalation was statistically significant. The bronchoconstrictive reaction pattern caused by challenge of the upper part of the airtract is probably different from this caused by challenge of the lower airways.

Histochemical and biochemical evaluation of complex carbohydrates in respiratory tissue of a canine model of allergic asthma

Ascaris hypersensitive dogs were chronically exposed to aerosols of this antigen under conditions designed to provide reproducible, pharmacologically manipulatable, pulmonary pathophysiology. As a partial characterization of this model the activities of several glycosyltransferases present in the respiratory tissue of these animals were investigated. In most cases, no significant difference from the levels found in respiratory tissues of unchallenged dogs was observed. The observation that in a few instances the activities of the UDP-Gal: mucin galactosyltransferase was significantly higher in the challenged dogs suggests that the tissue may have been operating at a near maximal capacity with respect to the synthesis of glycoproteins, and was, perhaps, approaching the point of initiating an increase in its synthetic capacity. Airways of ascaris-challenged dogs displayed little histochemical evidence of hypersecretion except in occasional tracheal glands filled with sulfomucin. However, the tracheal and bronchial glands of the experimental dogs revealed an increased prevalence of luminal casts that consisted of sulfated complex carbohydrate which partially filled some of the somewhat dilated acinar and ductal lumens. Abundant mast cells were present around peripheral vessels and bronchi, and into alveolar septae in lungs of the experimental dogs.

ROLE OF AFFERENT IMPULSES IN EXPERIMENTAL CONVULSIONS

ALTHOUGH clinical evidence on the effect of afferent impulses in either precipitating or preventing epileptic attacks has been presented since the time of Hughlings Jackson 1 (for more recent studies see Holmes, 2 Thomas 3 and Walshe 4 ), little experimental work has been done which throws light on the mechanisms involved. Franck 5 stated that stimulation of the occipital cortex may produce convulsive activity after the motor cortex has been sensitized through a previous stimulus which induced a convulsive seizure. These impulses seem to act on the motor cortex, since extirpation of the ipsilateral motor area prevents this effect (Rosenbach and Danillo 6 ). Franck stated also that stimulation of sensory nerves may precipitate seizures. Amantea 7 observed that movements can be evoked in dogs after a receptive zone in the sensorimotor cortex has been strychninized. Furthermore, he claimed that in hypersensitive dogs such stimuli may produce generalized convulsions. More recently,

Parenteral Denaturization of Foreign Proteins

Summary The accelerated denaturization of horse proteins in homologously hypersensitive dogs is due to some specific factor, the non-specific effect of sensitization being an inhibition or exhaustion of the normal, alien-protein denaturization function.

Relation of Protein Denaturization Rate to Specific Antibodies.

Horse proteins injected in routine doses intravenously into normal dogs are so completely denatured by the end of about 4 days that they no longer call forth recognizable anaphylactic reactions on massive blood transfusion into partially exsanguinated horse-serum-hypersensitive dogs.1 Representing this normal denaturization rate by the coefficient 1.0, the following approximate coefficients summarize our present data:Horse protein denaturization rate in:The rapid protein denaturization in hypersensitive dogs, therefore, is apparently due to some specific antibody which is absent or inoperative in immune dogs. This is best explained by the assumption that anaphylactic antibodies and immune antibodies are of different chemical compositions and of different physiological functions, both conceivably defensive in character.

Parenteral Denaturization of Foreign Proteins

Summary and Conclusions The rate of parenteral denaturization of horse proteins in horse serum immune dogs, therefore, is distinctly slower than the rate in normal dogs. There is not the rapid denaturization previously observed in hypersensitive dogs, all tests with hypersensitive donors being negative after the eighteenth hour (1). Nor is there the still more rapid denaturization one would predict from the unitarian conception of the relation of anaphylaxis to immunity. The biochemical properties or relationships responsible for rapid protein denaturization in hypersensitive dogs are apparently wholly absent or inoperative in immune dogs. This finding is consistent with our previous conclusion of the non-identity of specific antibodies in hypersensitive and immune dogs (3).

Persistence of Denatured Horse Proteins in the Canine Circulaton.

In previous papers1, 2 it was shown that horse proteins injected intravenously into normal dogs are retained quantitatively in the canine circulation for at least 6 days. During this retention, however, the proteins undergo marked denaturization. By the end of 4 days they will call forth no recognizable anaphylactic reaction even on massive transfusion into hypersensitive dogs. By the end of 6 days they cease to act as sensitizing agents for normal dogs. We have endeavored to follow subsequent changes in these proteins.Titration by means of a specific horse-protein-precipitating rabbit serum indicate that the proteins are further altered, denaturized or inhibited. By the end of 30 days they give little or no demonstrable reaction with rabbit precipitin, if tested in low dilutions.That this negative reaction is not due to an absence of horse proteins from the 30-day blood sample is indicated by continuing the titration to higher dilutions (Table I). In dilutions above 1:1000, the 6-day and 30-day samples g...

Passive Sensitization with Maignon's Fraction of Anaphylactic Blood.

In a recent paper Maignon reports the transmission of acquired hypersensitiveness in dogs by the injection of what we may tentatively call the proteose-peptone-amino-acid fraction of anaphylactic blood. We have attempted to confirm his findings. Maignon drew the blood of horse serum hypersensitive dogs directly into 4 volumes of 95% alcohol, dried and pulverized the resulting coagulum, extracted it with chloroform water, and reprecipitated with 95% alcohol. He obtained from each liter of anaphylactic blood about half a gram of a grayish white product. This product dissolved in physiological salt solution and injected into normal dogs rendered his dogs hypersensitive, the dogs giving apparently classical anaphylactic symptoms on subsequent intravenous injection with horse serum. We have applied Maignon's technic to 9 canine anaphylactic bloods and to emulsions of 6 hypersensitive livers. Eleven of the products thus obtained were wholly inert, giving no suggestion of passive hypersensitiveness even when injected in massive doses. Two of our blood products, however, and 1 liver product gave slight passive hypersensitiveness, and 1 blood product gave the severest anaphylactic phenomenon thus far observed in dogs. A kymograph record with this product is reproduced in Fig. 1. The symptomatology and autopsy findings with this product, however, were not those of typical anaphylaxis. The outstanaing symptoms were a sudden cessation of respiratory movements, accompanied by what was apparently an acute heart block. Death place in 4 minutes. The precipitous fall in arterial blood pressure, the characteristic feature of typical canine anaphylaxis, was wholly absent in this and in all of our other tests with Maignon's product On immediate autopsy the splanchnic area was found hyperemic The hyperemia, however, was of a bright arterial type, not the characteristic cyanotic engorgement of typical anaphylaxis.

Specificity of Hepatic Anaphylatoxins.

In previous papers, it was shown (a) that normal canine organs transplanted by blood vessel anastomosis into horse serum hypersensitive dogs are thrown into typical histamine-like reactions by the toxic products (anaphylatoxins) explosively formed or liberated by the hypersensitive liver during acute anaphylactic shock in the recipient. (b) That immune organs similarly transplanted are completely resistant to the histamine-like action of these hepatic products. And (c) that this acquired anaphylatoxin insusceptibility is not due to circulating antibodies, since it can not be transferred from one animal to another by even massive immune blood transfusion. We have thought to throw light on the nature of hepatic anaphylatoxins by a study of the specificity of this acquired fixed tissue anaphylatoxin resistance. To do this, tissue transplantations have been made between dogs immunized and sensitized with different antigens. The following is a summary of our results to date: (1) Urinary bladders of goat serum immune dogs, transplanted into horse serum hypersensitive dogs, show no suggestion of an acquired immunity to the hepatic anaphylatoxins explosively formed or liberated during acute horse serum shock in the recipient. (2) Horse serum immune urinary bladders, transplanted into goat serum hypersensitive dogs, show no suggestion of an acquired immunity to the hepatic anaphylatoxins explosively formed or liberated during acute goat serum shock in the recipient. From this it is evident that the hepatic anaphylatoxins are of different chemical nature in goat serum and horse serum anaphylaxis. This finding is in accord with our working hypothesis, that hepatic anaphylatoxins are specific secondary antigens of complex protein nature, presumably denaturization products of the primary antigens used in sensitization and immunization.