Interstitial inflammation

In a proportion of patients systemic and extra-articular features may be observed during the course of the disease (and rarely prior to joint disease). These include anaemia, weight loss, vasculitis, serositis, nodules in subcutaneous, pulmonary and sclera tissues, mononeuritis multiplex, and interstitial inflammation in lungs as well as in exocrine salivary and lacrimal tissue. However, these systemic manifestations occur relatively late in the disease progression. 

Little progress was made after these preliminary findings until 2004, when Lam et al. investigated the pulmonary toxicity of three types of SWNTs (raw HiPCO SWNTs, purified HiPCO SWNTs, and Ni-catalyzed arc discharge SWNTs) instilled in mice [58]. It was found that all three SWNT samples induced dose-dependent lung lesions and interstitial inflammation after 7 days. These lesions persisted and worsened after 90 days. 

Evaluation of the incidence data for nonneoplastic lesions in the NCI (1978) chronic oral study shows that there were statistically increased incidences of interstitial inflammation in the lungs of male rats. These rats were treated with 1,2-diphenylhydrazine in the diet at doses of 4 or 15 mg/kg/day for 78 weeks. Increased incidences of this lesion were also observed in female rats treated similarly with a dose of 2 mg/kg/day, but not in mice treated similarly with doses of 5.2 mg/kg/day (females), 10 mg/kg/day (males), or 52 mg/kg/day (males and females). The highest NOAEL value in mice and the LOAEL in rats for respiratory effects due to chronic exposure are recorded in Table 2-1 and plotted in Figure 2-1. 

In a 2-year inhalation study, rats and mice were exposed to 0, 67, 292, or 2056ppm 6 hours/day, 5 days per week. The major finding was a time- and dose-related increase in the incidence of kidney lesions in the male rats. These lesions consisted of cortical multifocal tubular basophilia (indicative of areas of cell regeneration), protein casts, and interstitial inflammation. There was epithelial cell shedding, and the casts were found within dilated renal tubules commonly at the corti-comedullary junction. 

Gn pig (NS) 4.5 yr 4 d/wk 4-5 hr/d Resp 1.6 (alveolar and interstitial inflammation alveolar hyperplasia, interstitial fibrosis) Steffee and Baetjer 1965 Mixed chromium roast K2Cr207, Na2Cr04 (VI)... 

Mouse Inhalation 20 ppm 24 h Minimal signs of irritation and behavior changes, questionable evidence of lung congestion and interstitial inflammation. Hine et al. 1970... 

In acute exposures, respiratory disease may be limited to interstitial inflammation of the alveolar epithelium, leading eventually to emphysema or pulmonary fibrosis (Cooper et al. 1982 Dungworth 1989 Stokinger 1981 Wedeen 1992). In studies of the pulmonary effects of airborne uranium dust in uranium miners and in animals, the respiratory diseases reported are probably aggravated by the inhalable dust particles (the form in which uranium is inhaled) toxicity because most of the respiratory diseases reported in these studies are consistent with the effects of inhaled dust (Dockery et al. 1993). In some of these instances, additional data from the studies show that the workers were exposed to even more potent respiratory tract irritants, such as silica and vanadium pentaoxide (Waxweiler et al. 1983). 

As the glomerular filtrate proceeds down the tubule, the filtrate becomes increasingly concentrated and the pH of the filtrate becomes more acidic. Therefore chemicals with pH-dependent solubility have the potential to precipitate and cause tubular obstruction, resulting in local interstitial inflammation, granuloma formation, and fibrosis. Indinavir is a protease inhibitor used in the treatment of immunodeficiency virus that has been reported to cause renal toxicity. The solubility of indinavir is pH- and flow-dependent, and some patients treated with indinavir form urinary crystals that obstruct tubules, leading to inflammation or granuloma formation, resulting in renal failure [23]. 

Eddy, A.A. Glachelll, C.M. Renal expression of genes that promote Interstitial Inflammation and fibrosis In rats with protein-overload proteinuria. Kidney Int 1995 47 1546-1557. 

From an epidemiological point of view, among the causes of AKI of a medical nature, drug-induced and toxic AKI are very important [77]. Nephrotoxic substances include a wide variety of compounds such as heavy metal ions, organic solvents, antibodies and natural toxins. Nephrotoxins induce AKI in humans by direct cellular toxicity, vasoconstriction, and crystal-mediated tubular obstruction. Acute interstitial inflammation is an important factor in pathogenesis of acute interstitial nephritis. In general, a decrement of... 

BIjukllc K, Jennings P, Kountchev J, HasslacherJ, Aydin S, Sturn D, PfallerW, Patsch JR, and Joannidis M. Migration of leukocytes across an endothelium-epithelium bilayer as a model of renal Interstitial Inflammation. Am J Physiol Cell Physiol 293 C486-492, 2007. 

Figure 3. Sequential renal biopsies, separated by 10 years, in a patient with hypokalemia related to chronic diuretic abuse. Initial biopsy (on the left) shows proximal tubular cell vacuolization and mild interstitial inflammation. The subsequen t examination (on the right) demonstrates marked interstitial fibrosis, tubular atrophy and dropout.

Acute phosphate nephropathy is commonly accompanied by mild to moderate interstitial inflammation composed of mainly lymphocytes. The interstitial inflammation is not associated with significant tubulitis and likely represents a response to the tubular injury and calcium phosphate deposition. Glomeruli typically appear unremarkable. Vascular disease is commonly encountered but is an expected finding given the mean age and high incidence of hypertension in patients with APhN. 

Li C, Yang CW, Park JFI, Lim SW, Sun BK, Jung JY, Kim SB, Kim YS, Kim J, Bang BK. Pravastatin treatment attenuates interstitial inflammation and fibrosis in a rat model of chronic cyclosporine-induced nephropathy. Am J Physiol Renal Physiol 2004 286 F46-57. 

Talcosis, caused by inhalation of pure talc, may include acute or chronic bronchitis as well as interstitial inflammation radiographically, it appears as interstitial reticulations or small, irregular nodules, typical of small airway obstruction. 

The interstitium of the kidney is also susceptible to injury from a variety of causes. Although acute interstitial nephritis is most commonly caused by medications (see Chap. 46), infections (e.g., streptococcal, leptospirosis, hantavirus, and human immimodeflciency virus), selected autoimmune disorders (systemic lupus erythematosus or mixed connective tissue disease) also may produce a similar syndrome. The presence of white blood cells (WBCs), WBC casts, and coarse granular casts in the urine aU suggest interstitial inflammation. The presence of eosinophUia and eosinophiluria also strongly suggest the presence of an interstitial nephritis. Occasionally low to moderate proteinuria can be seen on urinalysis. 

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