Numerous substances involved in mediating allergy (and inflammation) have been identified. The principal chemical mediators produced by mast cells and basophils are histamine, serotonin, leukotriene, platelet-activating factor, prostaglandins, and bradykinin (figure 1). These chemicals, acting alone or in combination, account for the tremendous scope of allergic symptoms. Targets of these mediators include the skin, upper respiratory tract, gastrointestinal tract, and conjunctiva. The general responses of these organs include rashes, itching, redness, rhinitis, sneezing, diarrhea, and shedding of tears. Systemic targets include smooth muscle, mucous glands, and nervous tissue. Because smooth muscle is re sponsible for regulating the size of blood vessels and respiratory passageways, changes in its activity can profoundly alter blood flow, blood pressure, and respiration. Pain, anxiety, agitation, and lethargy are also attributable to the effects of mediators on the nervous system.
Fig1. The spectrum of reactions to inflammatory cytokines released by mast cells and the common symptoms they elicit in target tissues and organs. Note the extensive overlapping effects.
Histamine is the most profuse and fastest-acting allergic mediator. It is a potent stimulator of smooth muscle, glands, and eosinophils. Histamine’s actions on smooth muscle vary with location. It constricts the smooth muscle layers of the bronchioles and intestine, thereby causing labored breathing and increased intestinal motility. In contrast, histamine relaxes vascular smooth muscle and dilates arterioles and venules. It is responsible for the wheal and flare reaction in the skin (see figure2), pruritis (itching), and headache. More severe reactions such as anaphylaxis can be accompanied by edema and vascular dilation, which lead to hypotension, tachycardia, circulatory failure, and, frequently, shock. Salivary, lacrimal, mucous, and gastric glands are also histamine targets.
Fig2. A method for conducting a skin test for type I allergies. The back (or forearm) is mapped and injected with a selection of allergen extracts. The allergist must be very aware of potential anaphylaxis attacks triggered by these injections. (a) View of skin prick test reactions for arthropod allergens, ranging from severe (spider) to 0 (caterpillar web). (b) A skin test record for some common environmental allergens in a patient with severe multiple allergies, some showing even more than 4+s. (a): Source: Dr. Frank Perlman, MA Parson/CDC
Although the role of serotonin* in human allergy is uncertain, its effects appear to complement those of histamine. In experimental animals, serotonin increases vascular permeability, capillary dilation, smooth muscle contraction, intestinal peristalsis, and respiratory rate, but it diminishes central nervous system activity.
A type of leukotriene, known as the “slow-reacting substance of anaphylaxis,” induces gradual contraction of smooth muscle. This leukotriene is responsible for the prolonged bronchospasm, vascular permeability, and mucous secretion of the asthmatic individual. Other leukotrienes stimulate the activities of polymorphonuclear leukocytes.
Platelet-activating factor is a lipid released by basophils, neutrophils, monocytes, and macrophages. The physiological response to this factor is similar to that of histamine, including increased vascular permeability, pulmonary smooth muscle contraction, pulmonary edema, hypotension, and a wheal and flare response in the skin.
Prostaglandins are a group of powerful inflammatory agents. Normally these substances regulate smooth muscle contraction. For example, they stimulate uterine contractions during delivery. In allergic reactions, they are responsible for vasodilation, increased vascular permeability, increased sensitivity to pain, and broncho constriction. Certain anti-inflammatory drugs work by preventing the actions of prostaglandins.
Bradykinin is related to a group of plasma and tissue pep tides known as kinins that participate in blood clotting and chemo taxis. In allergy, it causes prolonged contraction of the bronchioles, dilation of peripheral arterioles, increased capillary permeability, and increased mucus secretion.
