Macrophage reactions in septic arthritis.

With the aid of monoclonal antibodies, macrophages can be split into functionally distinct subpopulations on the basis of their phenotype. Absence of macrophage subtypes has been noted in chronic inflammatory processes, e.g. posttraumatic osteomyelitis, rheumatoid arthritis and sarcoidosis. In the inflammatory focus of acute septic arthritis (n = 13 patients) however, macrophages constitute the majority of immunocompetent cells. The inflammatory macrophage subtype 27E10 was clearly present in increased numbers in 11 of 13 biopsies from the inflammatory foci, showing the effector task of this subtype in synovial resistance. The anti-inflammatory macrophage subset RM3/1 was present in increased numbers in biopsies of infected tissue and the surrounding soft tissue. The occurrence of 25F9-positive macrophages, typical of the late phase of inflammation, varied widely in the biopsies.

Alteration in the pattern of macrophage subtypes in chronic osteomyelitis compared with acute joint infection.

Macrophage subtypes were detected in cryostat sections of biopsies from patients with chronic osteomyelitis, acute joint infections and normal bone marrow, using monoclonal antibodies against different macrophage populations. The resident macrophage subtype 25F9, the gluco-corticoid-inducible macrophage RM 3/1 and the inflammatory type 27E10 were found in abundance in acute infections. They were also present in tissue sections of uninflamed bone marrow. By contrast, in about 50% of the biopsies from patients with chronic osteomyelitis a reduced number of macrophage subtypes, or even the lack of one or more macrophage subpopulations was found. The unusual absence of macrophage phenotypes seems to be restricted to the area of osteomyelitis because in the tissues of inflamed sinuses in these patients, the macrophage subtypes were present. These findings suggest a disturbance at the level of the macrophages which may contribute to the persistence of the inflammatory process in osteomyelitis.

PMN elastase in bone and joint infections.

PMN (polymorphonuclear neutrophil) elastase is a proteolytic enzyme which is a biochemical marker for abnormal granulocyte stimulation. In inflammation and sepsis, excessive neutrophil stimulation results in significant amounts of PMN elastase being released into the plasma which indicates the severity of the disease and its prognosis. In 62 patients with osteomyelitis or suppurative arthritis, PMN elastase had a diagnostic sensitivity of 81%, which is comparable to the nonspecific erythrocyte sedimentation rate. Sensitivity of C-reactive protein (CRP) was 71%, fibrinogen 54% and leucocyte count 26%. PMN elastase was also useful in the follow up of patients with bone and joint infections; in the early post-operative period it became normal more quickly than the other findings unless the patients developed complications. Ten days after operation, PMN elastase was normal in 75% of the patients compared to the CRP which became normal in only 25%. Later both results were similar: on discharge from hospital, PMN elastase was normal in 77% and CRP in 71%.

[Lymphocyte defects in chronic osteomyelitis. A prospective study]. / Lymphozytendefekte bei der chronischen Osteomyelitis. Eine prospektive Studie.

In patients with chronic post-traumatic osteomyelitis, several deficits in immunological response were demonstrated. In a prospective trial of 20 patients with proven osteomyelitis, histological analysis of lymphocyte subsets in peripheral blood and in the infected bone tissue was performed. The effects of chronic osteomyelitis on lymphocyte subsets in the peripheral blood and in inflamed tissue were only slight. The T4/T8 ratio was diminished in only two patients and had no relationship to the clinical course. Interleukin 2 receptor determination was negative in 83% of biopsies of infected tissue. Osteomyelitis may possibly cause a defect in lymphocyte/macrophage cooperation.

[Suppression of macrophage subpopulations in post-traumatic osteomyelitis]. / Verminderung von Makrophagensubpopulationen bei der posttraumatischen Osteomyelitis.

Similar to other chronic inflammatory diseases such as rheumatoid arthritis the distribution of macrophage subtypes seems to be disturbed in post-traumatic osteomyelitis. This atypical distribution is clearly locally restricted in osteomyelitis. 27E10-positive macrophages found only during the acute phase of inflammation were reduced in 39%, the 25F9-positive subtype, predominating in the late stage of inflammation, was missing in 33%. The antiinflammatory macrophage RM3/1 was decreased in 40% of the osteomyelitis biopsies. Local suppression of macrophage subsets has to be discussed as one of the reasons for the persistence of chronic inflammatory processes in osteomyelitis.

[Immune reactions in chronic post-traumatic osteomyelitis. Current status determination]. / Immunreaktionen bei der chronischen posttraumatischen Osteomyelitis. Eine aktuelle Standortbestimmung.

Investigations in patients with chronic post-traumatic osteomyelitis could demonstrate several deficits in immunologic response: Phagocytic activity of phagocytes is lowered accompanied by a functional deminution of leukocyte receptors for C3. Intracellular killing is diminished. Investigations concerning T lymphocyte subpopulations verified a decrease in total T cells and helper/inducer T cells. Dysfunctions in specific humoral immune response are still debatable.

[PMN-elastase as a marker in diagnosis and follow-up of bone and joint infections]. / Die PMN-Elastase als Marker in der Diagnostik und Verlaufskontrolle von Knochen- und Gelenkinfektionen.

PMN elastase, a proteolytic enzyme, is a biochemical marker for pathologic granulocyte stimulation. In the presence of sepsis, excessive neutrophil stimulation occurs and significant amounts of PMN elastase are released into the plasma and serve as an indicator for the severity of the disease and the prognosis. PMN elastase is also a useful parameter for preoperative diagnostic management and postoperative follow-up of bone and joint infections. In patients with osteomyelitis and joint empyema (n = 48) PMN elastase had a sensitivity of 77%, which was only exceeded by that of the unspecific erythrocyte sedimentation rate (sensitivity 89%). Sensitivities of other inflammation parameters were lower: C-reactive protein (CRP) 67%, fibrinogen 50%, neopterin 32% and leukocyte count 21%. Determination of PMN elastase levels was also helpful in postoperative follow-up of patients with bone and joint infections. In the early postoperative period PMN elastase levels normalized more quickly than the other parameters unless patients actually developed complications. At the first postoperative determination (day 2-4 after surgery) 38% of the patients (n = 24) already had PMN elastase levels within the normal range (less than or equal to 40 micrograms/l) (CRP 13%). After 10 days PMN elastase was normal in 57% and CRP in 30% of the patients. Later on both parameters reacted similarly: by the time of discharge from hospital levels of PMN elastase were normal in 70% and CRP levels in 74%.