Table 1.
Immunostimulant and immunotoxic effects of unconjugated bilirubin (UCB) in cell primary cultures, cell suspensions, and animal models.
| Model | Cell | Effect | Reference |
|---|---|---|---|
| UCB | Polymorphonuclear leukocytes | ↓ Bactericidal activity | (Thong and Rencis 1977) |
| UCB | Polymorphonuclear leukocytes | ↓ Microbicidal function | (Thong and Rencis 1977) |
| UCB | Polymorphonuclear leukocytes | ↓ Fungicidal capacity | (Thong et al. 1979) |
| UCB | Cytotoxic T lymphocytes | ↓ Activity | (Haga et al. 1996a) |
| UCB | Lymphocytes | ↓ MHC-unrestricted cytotoxicity | (Haga et al. 1996b) |
| UCB | Astrocytes | ↑ Release of IL-1β, TNF-α, and IL-6 | (Fernandes et al. 2004) |
| UCB | Astrocytes | ↑ Activation of NF-κB and MAPK signaling cascades | (Fernandes et al. 2006, 2007a) |
| UCB | Microglia | ↑ Release of IL-1β, TNF-α, and IL-6 | (Gordo et al. 2006) |
| UCB | Microglia | ↑ Activation of NF-κB | (Silva et al. 2010] |
| ↑ Activation of MAPK Activation | |||
| ↑ Metalloproteinases 2 and 9 | |||
| ↑ COX-2 | |||
| UCB + LPS vs. UCB | Astrocytes | ↑ Necrosis | (Fernandes et al. 2004; Falcão et al. 2005] |
| ↑ TNF-α and IL-1β | |||
| UCB + LPS vs. UCB | Neurons | ↑ Apoptosis | (Falcão et al. 2007c) |
| ↓ Neurite extension | |||
| UCB + TNF-α vs. UCB | Neurons | ↑ Apoptosis | (Falcão et al. 2007c) |
| UCB + TNF-α + IL-1β vs. UCB | Neurons | ↑ nNOS | (Vaz et al. 2011b] |
| ↑ NO | |||
| ↑ Apoptosis (caspases 3, 8, 9 and tBid) | |||
| ↑ P-JNK1/2 | |||
| ↓ Viability | |||
| UCB | Bone marrow cell suspension | ↑ Apoptosis | (Khan and Poduval 2011) |
| ↑ Necrosis | |||
| UCB | Spleen cell suspension | ↑ Apoptosis | (Khan and Poduval 2011) |
| ↑ Necrosis | |||
| UCB injection | ↓ Viability of bone marrow cells | (Khan and Poduval 2011) | |
| ↓ Viability of splenocytes | |||
| ↓ Splenocyte proliferative response | |||
| ↑ p38MAPK activation | |||
| ↑ ROS | |||
| ↓ GSH | |||
| Mice model of intracerebral hemorrhage | ↑ Edema | (Loftspring et al. 2011) | |
| ↑ ICAM-1 expression | |||
| ↑ Neutrophil infiltration | |||
| ↓ Perihematomal microglia immunoreactivity | |||
MHC, major histocompatibility complex; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; NF-κB, nuclear factor-kappaB; MAPK, mitogen-activated protein kinase; COX-2, cyclooxygenase-2; LPS, lipopolysaccharide; nNOS, neuronal nitric oxide synthase; NO, nitric oxide; tBid, truncated BH3-interacting domain death agonist; P-JNK1/2, phospho-c-jun NH2-terminal kinase1/2; ROS, reactive oxygen species; GSH, reduced glutathione; ICAM-1, intercellular adhesion molecule-1.