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In order to understand events and mechanisms present in the pathophysiology of tilapia's chronic inflammation and based on the immunomodulatory activity attributed to cyclophosphamide which is widely used to suppress immune responses in human medicine, the present study investigated the effects of cyclophosphamide (CYP) treatment on the modulation of foreign body inflammatory reaction in Nile tilapia (Oreochromis niloticus) with round glass coverslip implanted in the subcutaneous tissue (9 mm of diameter). Forty tilapia (151 ± 10,2 g) were randomly distributed in 5 aquariums (n = 8) with a capacity of 250 L of water each, to compose two treatments (sampled 3 and 6 days post-implantation): implanted/untreated (control) and implanted/treated with 200 mg of CYP kg−1 of b.w., through i.p. route. A fifth group (n = 8) was sampled without any stimulus (naive) to obtain reference values. CYP-treated tilapia showed decrease in macrophage accumulation, giant cell formation and Langhans cells on the glass coverslip when compared to control fish. The treatment with CYP resulted in decrease of leukocyte and thrombocyte counts. Decrease in alpha-2-macroglobulin, ceruloplasmin, albumin and transferrin levels, as well as increase in haptoglobin, complement C3 and apolipoprotein A1 were observed in tilapias during foreign body inflammation. Blood levels of complement C3, alpha-2-macroglobulin, ceruloplasmin and transferrin were modulated by treatment with CYP. Therefore, the treatment with 200 mg of CYP kg−1 of b.w. in tilapia resulted in an anti-inflammatory effect by suppressing the dynamics between leukocytes in the bloodstream and macrophage accumulation with giant cell formation in the inflamed focus, as well as by modulating APPs during foreign body reaction. Image 1 • Anti-inflammatory effect was observed in CYP-treated tilapia. • Tilapia presented modulation of APPs during foreign body reaction. • Treatment with CYP suppressed macrophage accumulation and polykarion formation. • Tilapia treated with CYP showed decrease of leukocyte and thrombocyte counts. • Alpha-2-macroglobulin, ceruloplasmin and transferrin were modulated by CYP. [ABSTRACT FROM AUTHOR]

In order to understand the pathophysiology of melanomcrophage centers (MMCs) formation during the tilapia defense response to bacterial infections, the present study evaluated the response, in terms of area, number and pigment constitution, of splenic MMCs of Oreochromis niloticus subjected to intraperitoneal (i.p.) infection with Aeromonas hydrophila and Mycobacterium marinum. Eighty-four fish (396.9 ± 21.0 g) were randomly distributed into twelve plastic tanks (300 L), to constitute three treatments with 28 animals each: control group (inoculated with PBS); Infected with A. hydrophila (1 × 107 UFC mL−1); Infected with M. marinum (1 × 106 UFC mL−1). The spleen was collected in seven fish per treatment on the 3rd, 7th, 14th and 21st day post-infection (DPI). The results revealed the participation of MMCs in the defense response of tilapia during bacterial infection by A. hydrophila and M. marinum , since there was an increase in the number and size of these cell aggregates. Variation of pigment accumulation with significant increase of hemosiderin, in infected tilapias by A. hydrophila , bacteria responsible for causing hemolytic anemia in fish was also found. On the other hand, M. marinum -infected tilapia had high amount of melanin in MMCs. In general, mycobacterial infections are notoriously difficult to treat, being characterized as a chronic disease. These findings demonstrate different strategies of fish response during the evolution of these bacterial diseases. Image 1 • There was an increase in the area of the MMCs in infection with A. hydrophila and M. marinum , mainly in the 14 and 21 DPI. • Apart from mode of infection manifestation (acute and chronic), tilapia responses were similar after infection. • Perls' staining demonstrated that the MMCs in all the groups contained hemosiderin and melanin. • Tilapia infected with M. marinum showed higher levels of melanin pigment when compared to A. hydrophila infected fish. • Responsible for causing hemolytic anemia in fish, A. hydrophila infection resulted in increase of hemosiderin pigment. [ABSTRACT FROM AUTHOR]