Cause of idiopathic sudden sensorineural hearing loss: The stress response theory

Table 3 Nuclear factor κ-light-chain-enhancer of activated B cells activation and associated cytokine expression in the lateral wall

Animal	Stressor	Time point	NF-κB		Other factors			Ref.
			Response	Location	Factor	Response	Location
CBA/CaJ mice	LPS, ip	24 h	Activation	Unilateral, II >> I, Lim.				[141]
	LPS, ip + dexamethasone, ip		No activation
	Anti-CD3, ip		Activation	I
	Taxol, ip		Activation	I
	100 dB SPL		Activation	Bilateral, I >> II, Lim.
CBA mice	117 dB SPL	4 h	Transcription	LW				[142]
		2-12 h1 (4 h)			iNOS	Transcription	LW
		0-12 h (6 h)			ICAM-1	Transcription	LW
		2-12 h (6 h)			VCAM-1	Transcription	LW
		14 h			ICAM-1	Expression	SV
		14 h			VCAM-1	Expression	SV
Swiss-Webster mice	Ag	7 d			Leukocytes	Expression2	SL3	[143]
	90 or 100 dB SPL	7 d				No expression
	90 or 100 dB SPL + Ag	7 d				No expression
	118 dB SPL	4 h	Activation	I, II, IV
		7 d	No activation		Leukocytes	Expression2	LW
					ICAM-1	Expression	II
	118 dB SPL + Ag	4 h	Activation	I, II, IV, HC, SC
		7 d	Activation	HC, SC	Leukocytes	Expression	LW4
			Activation		ICAM-1	Expression	II, III >> I4
C57/Bl6J mice	124 dB SPL	2 h	Activation	I, II, III, IV, SV	iNOS	Most of NF-κB activated cells		[144]
		72 h	Activation	I, II, III, IV, SV5	iNOS	Most of NF-κB activated cells5
Sprague-Dawley rats	Cisplatin, ip	24 h	Activation	I, II, III, IV, SV, OHC, Lim.	IL-1β	Expression	II, IV >> I, III, SMV	[145]
					IL-6	Expression	SMV
					TNF-α	Expression	I, II, III, IV, SV, Lim., SMV, HC
	Cisplatin + TNF-α inhibitor		No activation		IL-1β	No expression, no transcription
					IL-6	No expression, no transcription
					TNF-α	No expression, no transcription
Sprague-Dawley rats	124 dB SPL	3 h			IL-6	Expression	III, IV	[146]
		6 h				Expression	I, II, III, IV
		12 h				Expression	I, II, III, IV, SV, SG
		24 h				Expression	I, II, III, IV, SG6

¹The time in the parentheses is the time of the maximum up-regulation of a factor;

²The paper did not show whether it was significant or not in only the lateral wall, although it was significant in the total number of leukocytes in the modiolus, spiral limbus (Lim.), spiral ligament (SL), stria vascularis (SV), and the scala tympani. However, the number in the lateral wall showed a clear tendency of increase compared with controls;

³There were a small number of leukocytes in the spiral ligament;

⁴The leukocyte number and the intercellular adhesion molecule 1 (ICAM-1) expression intensity were significantly more than those of Ag alone and 118 dB noise alone in the total of modiolus, Lim., SL, SV, and the scala tympani;

⁵The intensity at 72 h was weaker than at 2 h;

⁶The intensity at 24 h was much weaker than at 12 h in the lateral wall. Some papers demonstrated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation in the lateral wall and cytokine expression. The systemic stressors that induce stress response of the lateral wall are shown in the column “Stressor”. Each paper used different methods and time points to observe the response. For example, the activation of NF-κB (Activation) (i.e., translocation of NF-κB from the cytoplasm into the nucleus), its transcriptional up-regulation (Transcription), and the protein expression (Expression) were analyzed. Some papers demonstrated which types of cells responded to stressors in the lateral wall, but some did not. Noise was band noise for 2 h in all experiments, and the intensities are shown in the table. I-IV, type I-IV fibrocytes in the lateral wall; II >> I, The NF-κB activation was much stronger in type II fibrocytes than type I fibrocytes; Ag, An adaptive inner ear immune response was created by sensitizing mice to the keyhole limpet hemocyanin. Then, the mice were sensitized systemically to the antigen in experimental conditions shown as Ag or + Ag in the table. iNOS: Inducible nitric oxide synthase; ip: Intraperitoneal injection; LPS: Lipopolysaccharide; LW: The transcriptional up-regulation or the protein expression was observed in the lateral wall: but the specific cell type was not determined; SC: Supporting cell; SMV: Spiral modiolar vein; VCAM-1: Vascular cell adhesion molecule 1; IL: Interleukin; TNF-α: Tumor necrosis factor α; HC: Hair cell; OHC: Outer hair cell.