|A pharmacological basis for anti-inflammatory therapy
Dr. Jeff R. Wilcke, DVM, MS, DACVCP
Virginia Maryland College of Veterinary Medicine
The benefits and risks of anti-inflammatory therapy go hand in hand. Efforts to manipulate inflammatory mediators result in changes to "other" homeostatic processes. To control inflammation, it may be necessary to tolerate adverse effects. The response to anti-inflammatory therapy is unique to each combination of patient and condition, and may well change as the case progresses.
|Figure 1. Inflammatory cascade. Different types of inflammation trigger different portions of the cascade. Immunomodulators may not have a role if the inflammation is "local". Glucocorticoid (steroid) agents may have a role in either immune or local inflammatory responses. NSAID agents may control some clinical signs of immune-mediated diseases, but they are not used as sole agents for treatment.|
|Inflammatory stimulus - red arrow|
Cytokine or action - blue arrow
Site of action (all members of class) Green solid arrow
Site of action (some members of class) Green dashed arrow
NSAIDs and glucocorticoid (steroid) hormones are the two most common classes of agents used to deal with "simple" inflammation. The are referred to here as "direct" because they directly affect production or prostaglandins and leukotrienes, primary mediators in "local" inflammtion. Table 1 compares clinically relevant features of these two classes.
|Clinical "endpoint"||NSAID (class)||Glucocorticoid (class)|
|Reduce inflammation||modulate inflammation a local environment||modulate cellular responses to immune and inflammatory stimuli|
||No analgesia except controlling inflammation can lead to reduced pain stimulus.|
|Fever||Fever reduction is independent of anti-inflammatory activity||Only antipyretic secondary to reduced concentrations of cytokines.|
|Mood / cognition||No direct effects on cognitive function||improve mood and sense of well-being independent of other effects|
|Adverse effects||Blocking production of prostaglandins required for "homeostasis" produces most toxicities.||Few acute or immediately life-threatening adverse effects.
ALL patients suffer side effects if duration of therapy is long. ("Chronic use")
|Consequences of inappropriate use||NSAIDS may interfere with:
||Glucocorticoids may interfere with:
Anti-inflammatory immunomodulators reduce immune-based stimulation of the inflammatory cascade. They may either do this by altering the production of cytokines or by depressing populations of immune cells.
Certain agents are considered to be anti-inflammatory and act through novel (and difficult to prove) mechanisms (DMSO, superoxide dismutase) or by mitigating the response of certain tissues to inflammation (PSGAGs for arthritis).