IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses.

IL-6 is induced often together with the proinflammatory cytokines TNFalpha and IL-1 in many alarm conditions, and circulating IL-6 plays an important role in the induction of acute phase reactions. However, whether this endogenous IL-6 plays any additional pro- or antiinflammatory roles in local or systemic responses remains unclear. In this study, the role of IL-6 in acute inflammatory responses was investigated in animal models of endotoxic lung or endotoxemia by using IL-6+/+ and IL-6-/- mice. Aerosol exposure of endotoxin induced increased IL-6 and proinflammatory cytokines TNFalpha and MIP-2 and a neutrophilic response in the lung of IL-6+/+ mice. However, the levels of TNFalpha and MIP-2 and neutrophilia were significantly higher in the lung of IL-6-/- mice. The rate of neutrophil apoptosis in these mice was similar to that in IL-6+/+ mice. A low constitutive level of antiinflammatory cytokine IL-10 was not enhanced by endotoxin and remained similar in the lung in both IL-6+/+ and IL-6-/- mice. Systemically, intraperitoneal delivery of endotoxin resulted in much more pronounced circulating levels of TNFalpha, MIP-2, GM-CSF, and IFNgamma in IL-6-/- mice than in IL-6+/+ mice, and administration of recombinant IL-6 to IL-6-/- mice abolished these differences. In contrast, circulating IL-10 levels were induced to a similar degree in both IL-6+/+ and IL-6-/- mice. Thus, our studies reveal that endogenous IL-6 plays a crucial antiinflammatory role in both local and systemic acute inflammatory responses by controlling the level of proinflammatory, but not antiinflammatory, cytokines, and that these antiinflammatory activities by IL-6 cannot be compensated for by IL-10 or other IL-6 family members.

Emphysematous pyelonephritis. Complicated urinary tract infection in diabetes.

Renal emphysema is rare condition that may affect diabetic patients. Radiographic demonstration of gas limited to the collecting system is often treated with antibiotics. However, intraparenchymal gas requires early nephrectomy because mortality rates are high without surgical intervention.

The use of antimicrobial drugs in office practice.

Antimicrobial drugs are used extensively, but not well. Widespread and indiscriminate use of these drugs encourages the development of antibiotic resistance. Before prescribing an antimicrobial drug, physicians should ask themselves whether prophylactic or empirical therapy is justified, what is (are) the most likely micro-organism(s) involved, what is the best antimicrobial drug for this patient, and what is the optimal dosage and duration of treatment. The penicillins, erythromycin, tetracycline, cephalosporins, sulfonamides, cotrimoxazole and trimethoprim are discussed in the light of these questions.

Drug treatment of cardiac failure.

Treatment of cardiac failure should first be aimed at reversing or ameliorating the underlying pathological processes. This review highlights the common problems and pitfalls in the use of digoxin, diuretics and vasodilators in patients with cardiac failure.

Meningococcal infections in the Hamilton area during 1978.

During 1978 there was a marked increase in the number of patients with meningococcal infection in the Hamilton area. Of 21 patients admitted to St. Joseph's Hospital, Hamilton, two thirds were under 5 years of age. Four patients died. All the isolates were sulfonamide-sensitive strains of serogroup B Neisseria meningitidis. Although no infections developed in contacts, several errors were made in the management of the hospital and household contacts of the infected patients: chemoprophylaxis was given to many contacts not considered to be at risk; ineffective antibiotics, particularly penicillin, were given for chemoprophylaxis; and chemoprophylaxis was often delayed while the results of cultures of nasopharyngeal and throat secretions were awaited. Circulation to local physicians of guidelines on proven prophylactic regimens was followed by a reduction in the frequency of these errors.

Septic shock.

Septic shock is a dynamic syndrome of inadequate tissue perfusion caused by invasion of the blood by micro-organisms. Gram-negative rod bacteremia accounts for about two-thirds of patients with this syndrome. The fully developed syndrome of high fever, chills, cold, moist extremities, hypotension and oliguria is easy to recognize. However, the initial features of the syndrome may be quite non-specific and subtle, particularly in elderly patients. Treatment is aimed at eliminating the infection, improving tissue perfusion, supporting ventilation and managing specific complications.

Respiratory tract infections in adults.

Most upper respiratory tract infections are caused by viruses, but recognition of the cause of a particular illness is impossible based on clinical findings alone. Epiglottitis caused by type B Hemophilus influenzae can occur in adults with the same threat to upper airway obstruction as in children. An approach to the diagnosis of pneumonia is outlined and pneumonias caused specifically by viruses, mycoplasma, and bacteria are described.

Prescribing of psychoactive drugs for chronically ill elderly patients.

The prescribing of psychoactive drugs for 1431 chronically ill elderly patients being assessed for long-term institutional or community care was surveyed. Psychoactive drugs had been prescribed for about one quarter of the patients; benzodiazepines were the most frequently prescribed group. Judging from the extensive prescribing of flurazepam and chloral hydrate, commonly used hypnotics, the main reason psychoactive drugs were prescribed was to provide night-time sedation. Antidepressants and drugs promoted as useful in improving cognitive function were infrequently prescribed. Commendable prescribing practices included the infrequent use of "cerebral vasodilators" and barbiturates. Questionable prescribing practices included the infrequent use of tricyclic antidepressants in severely depressed patients and the use of tranquilizers in patients described by their attending physician as markedly or extremely withdrawn.